Visceral Metastases Research Articles

Prognostic Implications of 68Ga-FAPI-46 PET/CT-Derived Parameters on Overall Survival in Various Types of Solid Tumors.

Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [68Ga]Ga-fibroblast activation protein inhibitor (FAPI) (68Ga-FAPI)-46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, n = 30; NCT04571086, n = 115). Methods: Within 4 wk, 145 patients underwent 68Ga-FAPI-46 and [18F]FDG (18F-FDG) PET/CT. The association between overall survival (OS) and sex, age, tumor entity, total lesion number, highest SUVmax, and the presence of each nodal, visceral, and bone metastasis was tested using univariate Cox regression analysis. Multivariate analyses were performed for prognostic factors with P values of less than 0.05. Results: In the univariate analysis, shorter OS was associated with total lesion number and the presence of nodal, visceral, and bone metastases on 68Ga-FAPI-46 PET/CT (hazard ratio [HR], 1.06, 2.18, 1.69, and 2.05; P < 0.01, < 0.01, = 0.04, and = 0.02, respectively) and 18F-FDG PET/CT (HR, 1.05, 2.31, 1.76, and 2.30; P < 0.01, < 0.01, = 0.03, and < 0.01, respectively) and with SUVmax on 68Ga-FAPI-46 PET/CT (HR, 1.03; P = 0.03). In the multivariate analysis, total lesion number on 68Ga-FAPI-46 PET/CT was an independent risk factor for shorter OS (HR, 1.05; P = 0.02). In patients with pancreatic cancer, shorter OS was associated with total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.09; P < 0.01) and bone metastases on 18F-FDG PET/CT (HR, 31.39; P < 0.01) in the univariate analysis and with total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.04) in the multivariate analyses. In breast cancer, total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.02), as well as bone metastases on 18F-FDG PET/CT (HR, 9.64; P = 0.04), was associated with shorter OS in the univariate analysis. The multivariate analysis did not reveal significant prognostic factors. In thoracic cancer (lung cancer and pleural mesothelioma), the univariate and multivariate analyses did not reveal significant prognostic factors. Conclusion: Disease extent on 68Ga-FAPI-46 PET/CT is a predictor of short OS and may aid in future risk stratification by playing a supplemental role alongside 18F-FDG PET/CT.

A Rare Tumor of Scalp - Giant Multiple Cellular Histiocytofibroma

Histiocytofibroma or dermatofibroma is a rare benign cutaneous tumor present preferentially in the dermis. Histiocytofibroma is most frequent benign tumor, but some specific morphological forms may present local recurrences and can cause lymph node and visceral metastases. The trunk and limbs represent the most classically described topography, other locations are known like face and scalp. Histiocytofibroma is most often present as a unique lesion: papule or nodule, giant form is not common and it is characterized by a large tumor volume (5 cm or more). The cellular histological variant is a rare subtype. We report a case of a 56-year-old male patient with no particular past medical history, who presented with a fronto-parietal cutaneous large tumor evolved for 2 years, gradually increasing in volume, measuring 7 cm in diameter, with regular contours, flesh colored, and peripheral vascularization on the surface of the lesion, it was firm and adherent to bone plane at palpation, along with seven other small lesions, the largest of which was 2 cm. The CT scan did not show any bone invasion. Surgical management consisted of large excision with 1 cm free margins. histological and immunohistochemical findings were in favor of cellular histiocytofibroma. The substance loss was covered by skin graft after complete budding. A 26 months follow up results were good without recurrence.

Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

Outcomes and patterns of use of Radium-223 in metastatic castration-resistant prostate cancer.

Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15months (interquartile range: 1-56months). The median age at diagnosis was 49years (range: 35-90years). The estimated mPFS was 6.0months (95%CI 5.3-7.8months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18months (8.7months, 95%CI 6.6-11.3months), in patients w/o visceral metastases (8.0months, 95%CI 5.8-10.5months), and chemotherapy-naïve in the metastatic setting (7.2months, 95%CI 5.9-8.4months). This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Abstract PO1-16-02: Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC)

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC &amp;lt; 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were &amp;lt; 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p&amp;lt; 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P&amp;lt; 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (&amp;lt; 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs &amp;lt; 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-02.

Abstract PO4-04-10: Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial

Abstract BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard of care for hormone receptor-positive (HR+)/Human Epidermal Growth Factor 2 negative (HER2-) metastatic breast cancer (MBC); no consensus actually exists for second-line (2L) treatments. The HERMIONE-13 trial evaluates the adopted therapeutic options after CDK4/6i failure and the potential factors that influence these choices. METHODS: HERMIONE-13 is a retrospective and prospective multicentric observational trial involving 15 Italian Centers. Information about therapies after disease progression to CDK4/6i from January 2016 until December 2020 was collected for the present analysis, aiming at evaluating which are the clinical criteria guiding the choice of 2L therapy after CDK4/6i failure. RESULTS: 114 pts have been enrolled: 14 pts (12.3%) received neoadjuvant treatment, 80 (70.2%) adjuvant therapy, of whom 46 (57.5%) chemotherapy (CT)+ endocrine therapy (ET) and 33 (41.3%) ET alone. Among the 79 pts treated with adjuvant ET, 44 pts (55.7%) showed primary or secondary endocrine resistance. 39 pts (34.2%) received first-line (1L) CDK 4/6i in combination with Fulvestrant (F), the remaining with aromatase inhibitors (AIs). Median duration of 1L CDK4-6i was 10.4 months (interquartile range (IQR) 4.7-17.4). Median age at 2L start was 59.5 years (IQR 51-68). As 2L therapy, 79 pts (69.3%) received CT±targeted therapy (TT) and 35 (30.7%) ET±TT. Visceral metastases at the beginning of 2L were documented in 46 pts (40.4%). Comorbidities were present in 48 (42.9%) of the pts, mainly cardiac diseases (25, 22.3%); 71 pts (63.4%) showed a 1L-related adverse events (AEs) (NA: 2 pts), mainly hematological toxicity (60, 53.6%). Among 79 pts treated with adjuvant ET, 60 (76%) were addressed to 2L CT±TT, while 19 (24%) to an ET-based therapy. A longer duration of 1L was observed in pts treated with 2L ET±TT (12.5 months, 7.2-22.2) in comparison with those treated with CT±TT (8.7 months, 4.2-14.9). The majority of pts treated with 1L F+CDK 4/6i underwent 2L CT-based treatment, as summarized in Table 1. Analyzing the population treated with 2L CT±TT, we observed that median age was 58 years (49-67), slightly lower than that of pts treated with ET±TT (63, 54-69). Among pts with visceral metastases, 30 pts (65.2%) were addressed to 2L CT±TT and 16 pts (34.8%) to ET±TT; CT±TT was also the favorite choice for the majority of pts with concomitant disease (33, 68.8%) and with previous CDK4/6i-related toxicity (47, 66.2%). Among age, visceral metastases, comorbidities, adjuvant treatment, duration of 1L therapy, use of 1L F and 1L related AEs, univariate analysis revealed that previous use of adjuvant ET (p=0.021), 1L F (p&amp;lt; 0.001), duration of 1L treatment (p=0.043) and age at 2L start (p=0.053) are all factors influencing the choice of 2L therapy. At the multivariate logistic regression model, only the use of F in association with CDK4/6i as 1L treatment and age at 2L therapy were associated with the choice between ET±TT vs CT± TT, with a backward selection, as summarized in table 2. CONCLUSION: The preliminary results of our study suggest that previous F in combination with CDK4/6i is a statistically confirmed predictor of choice for subsequent CT, whereas the increase in age is significantly associated with the choice for ET. Further research is needed to investigate the optimal sequencing of treatments following CDK4/6i and to determine predictive factors of response to 2L therapies. Table 1 2L choices in 1L F+CDK 4/6i pts. Table 2 Statistical model with the significant variables. Citation Format: Marina Elena Cazzaniga, Emanuela Rossi, Antonella Turla, Massimo Ambroggi, Alice Baggi, Rossana Berardi, Fulvio Borella, Serena Capici, Federica Cicchiello, Luigi Coltelli, Ugo De Giorgi, Antonella Ferro, Ornella Garrone, Monica Giordano, Elisabetta Landucci, Marco Mazzotta, Gabriella Moretti, Raffaella Palumbo, Francesca Fulvia Pepe, Patrizia Vici, Fable Zustovich, Viola Cogliati. Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-10.

Abstract PO3-17-02: Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P&amp;lt; 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-02.

Abstract PO2-04-12: From Clinical Trials to Clinical Practice; Real World Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2- Negative Metastatic Breast Cancer

Abstract Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor-2 (HER2)-negative metastatic breast cancer (MBC), with an impressive efficacy and safety profile. Here we report real-world clinical outcomes and toxicity data in patients treated at a tertiary care cancer center. Methods: The study is a retrospective analysis of individual patients’ data. All consecutive patients with HR+ and HER2-negative MBC, treated at our institution with ribociclib plus aromatase inhibitors (AI) or fulvestrant, between June 2017 and May 2020 were reviewed. Data were collected from patients’ electronic medical records. Progression free survival (PFS) was defined as the time from treatment initiation with CDK4/6i until the first documented progression, death from any cause or last follow-up, whichever occurred first. The Overall survival (OS) was defined as the time from treatment initiation with CDK4/6i until the date of death from any cause, or last follow-up. Results: A total of 305 patients, median age 49 (22-87) years were enrolled. Although bone metastasis was reported in 241 (79.0%) patients, bone-only metastasis was identified in 64 (20.9%). Visceral metastasis in the liver and lungs were reported in 22.0% and 25.9 % of patients, respectively. CDK4/6i combined with AI were used in first-line setting in 195 (63.9%) patients and with fulvestrant as a second line (20.7%) or beyond (15.4%). Dose reduction was required in 44 (14.14%) patients, mostly because of neutropenia (n=38, 12.5%) and abnormal liver enzymes (n=12, 3.9%), while 11 (3.6%) discontinued treatment, mostly due cardiac toxicities. Nevertheless, there were no deaths due to toxicity. Patients were followed up for a median of 31.1 months. Overall response rate (ORR) was 51.4% and median PFS, irrespective of the line of therapy, was 19.3 (17.6-23.3) months. PFS was longer in first-line setting; 23.1 (19.7-NR) months compared to 13.9 (10.2-17.6) months in second-line or beyond, p&amp;lt; 0 .0001, and when combined with AI compared to fulvestrant; 28.6 (17.8-23.1) months versus 9.1 (4.4-NR) months, p=0.0001, and in those with bone-only metastasis; 23.1 (19.5-NR) months versus 17.3 (12.2-18.9) months for patients with visceral metastasis, p=0.0008. The median OS was not reached. Conclusions: Despite enrolling sicker patients, and outside the stringent clinical trials settings, our treatment outcomes, in real world settings, are comparable to those reported in major clinical trials, including MONALEESA-2, MONALEESA-3 and MONALEESA-7. Citation Format: Baha' Sharaf, Faris Tamimi, Sarah Edaily, Osama Salama, Hazem Abdulelah, Anas Zayed, Mahmoud Abunasser, Hala Abu-Fares, Hikmat Abdel-Razeq. From Clinical Trials to Clinical Practice; Real World Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2- Negative Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-12.

Abstract PO2-06-06: Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC

Abstract Background The optimal choice of drug is important in treating metastatic breast cancer, and the efficacy of the drug should be determined early, especially in cases of progression. On the other hand, untreated de novo Stage IV (dnST-IV) patients are expected to be more sensitive to drugs, but no detailed data are available. In JCOG1017 (Randomized trial of primary tumor resection in dnST-IV), dnST-IV patients were treated with primary systemic therapy for 3 months according to breast cancer subtypes before randomization. We already presented the results of primary endpoint. Primary tumor resection (PTR) could not significantly prolong the overall survival of de-novo stage IV breast cancer patients with sensitivity to primary systemic therapy. We conducted the supplementary analysis of JCOG1017 to clarify the efficacy of primary systemic therapy for dnST-IV and develop optimal treatment strategies for dnST-IV breast cancer. Methods In JCOG1017, systemic therapy was performed for each subtype/metastatic status as follows; 1) hormone therapy: ER+ HER2- and no life-threatening metastases, 2) weekly PTX therapy: life-threatening metastases, or ER-HER2-, 3) trastuzumab + pertuzumab + docetaxel (HPD) therapy OR trastuzumab + paclitaxel (HPTX) therapy: ER-HER2+. 4) hormone therapy: ER+HER2+ and no life-threatening metastases. The non-PD rate (no increase of more than 10% of the sum of the diameters of the target lesions compared before systemic therapy), the responses rate (cCR or cPR), and overall survival (OS) of responder (cCR or cPR)/non-responder (cSD or cPD) and PD/non-PD were examined. Results Among 569 patients who received primary systemic therapy in JCOG 1017, the non-PD rate was 77.2% and the response rate was 29.0% after 3 months of systemic therapy. By subtype, the non-PD rate was 78.2% for ER-HER2-, 75.4% for ER+HER2-, 92.9% for ER-HER2+, and 66.7% for ER+HER2+. The response rate was 36.4% for ER-HER2-, 13.4% for ER+HER2-, 81.0% for ER-HER2+, and 40.3% for ER+HER2+. In multivariable analysis, the non-PD rate was higher in postmenopausal (odds ratio [OR] 1.673, p=0.0240) and PgR-positive (OR 2.391, p= 0.0019) patients besides subtypes. Analysis results by drug were as follows; 1) hormone therapy (non-PD rate: 72.9%) was more effective for PgR-positive (OR 3.258, p&amp;lt; 0.0001), less effective for patients with visceral metastasis (OR 0.605, p=0.0334) and HER2-positive (OR 0.365, p=0.0016), 2) wPTX (non-PD rate: 76.1%) was no significant predictors of efficacy, 3) HPD/HPTX (non-PD rate: 92.7%) was more effective in patients with visceral metastasis (OR 15.818, p=0.0030). PD patients had much worse OS (hazard ratio [HR] 0.501, p&amp;lt; 0.0001) compared to non-PD, whereas responders had a little worse OS (HR 0.788, p=0.0538) compared to non-responders. Similar tendency was observed in any drug. Discussion Predictors of response to primary systemic therapy differed by subtype, with the need for treatment strategies tailored to PgR, HER2 expression, and the status of visceral metastasis. In the ER+HER2+ group, the efficacy of hormonal therapy alone was low, and combination therapy with molecular-targeted agents was considered necessary. The non-PD rate reflected prognosis in determining the efficacy of primary systemic therapy for dnST-IV. Citation Format: Tadahiko Shien, Akihiko Shimomura, Makoto Ishitobi, Kiyo Tanaka, Takahiro Tsukioki, Takashi Yamanaka, Fumitaka Hara, Kenjiro Aogi, Yasuhiro Yanagita, Michiko Tsuneizumi, Naohito Yamamoto, Hiroshi Matsumoto, Akihiko Suto, Ken-ichi Watanabe, Michiko Harao, Chizuko Kanbayashi, Mitsuya Ito, Keisei Anan, Shigeto Maeda, Keita Sasaki, Gakuto Ogawa, Haruhiko Fukuda, Hiroji Iwata. Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-06.

Abstract PO1-29-02: Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer

Abstract Background: KN026 is a novel bispecific HER2-targeted antibody. Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab and pertuzumab. Preliminary safety and efficacy results (data as of Aug 18, 2022) were presented at SABCs 2022(PD18-08), showed promising efficacy and tolerability. Herein, we update the 2.5-year follow-up results. Methods: Eligible subjects with recurrent/metastatic breast cancer, HER-2 positive and treatment-naive were enrolled. Subjects received KN026 30 mg/kg combined with docetaxel 75 mg/m2 Q3W until disease progression, unacceptable toxicity, or other reasons. The primary endpoints were ORR and DoR. The secondary endpoints included safety, PFS and OS. Results: As of data cut-off date (Sep 15, 2023), 57 subjects were enrolled, the median age was 52 years (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV. There were 34 and 23 subjects with and without visceral metastasis, respectively. 48 subjects with high HER2 expression (IHC 3+), and the other 9 subjects with HER2 expression 2+ or 1+. The confirmed ORR within 55 evaluable subjects was 76.4% (42/55). The DoR was not reached yet with a median follow-up of 27.0 mons (95% CI: 26.28, 28.98). The median study follow-up was 30.6 mons (95% CI: 29.11, 31.77). The mPFS was 27.7 mons (95% CI:17.97, NE) and the mOS was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.2% (95% CI: 71.85, 91.45) and 78.5% (95% CI: 65.25, 87.21). The mPFS of subjects with or without visceral metastasis were 23.6 mons and not reached. The mPFS of subjects with or without brain metastasis were 13.7 mons and 28.1 mons, respectively. The mPFS of 48 subjects with high HER2 expression (3+) was 28.1 months. The incidence of KN026-related Grade≥3 TRAE was 43.9% (25/57), including neutrophil count decreased 24.6% (14/57), white blood cell count decreased 12.3% (7/57), hypokalaemia 7.0% (4/57), diarrhoea 3.5% (2/57) and others less than 2%. The incidence of serious adverse events related to KN026 was 12.3% (7/57). There was no KN026 -related death. Conclusions: KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2.5 years follow-up, mPFS was 27.7 mons and the 24-months OS rate was 84.2%, which is very promising. No new safety signals were observed. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control. Citation Format: Qingyuan Zhang, Jingxuan Wang, Quchang Ouyang, Xiaojia Wang, Jingfen Wang, Lu Gan, Daren Lin, Zhong Ouyang, Ting Xu, Yilan Liu, Yuan Lv. Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-02.

Abstract PO4-04-07: Efficacy, safety and translational study of pyrotinib combined with albumin-bound paclitaxel as firstline treatment of HER-2 positive metastatic breast cancer

Abstract Objective: Breast Cancer is one of the most common malignant tumors in women. HER-2 is a driver gene for poor prognosis in breast cancer. Anti-HER-2 drugs have significantly improved the prognosis of patients with HER-2 positive metastatic breast cancer. There is still a lack of exploration of first-line anti-HER2 treatment options and translational studies only for patients with metastases after adjuvant and/or neoadjuvant trastuzumab therapy. This study is based on our previous clinical trial of pyrotinib in combination with albumin-bound paclitaxel in first line for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy, with the aim of exploring the efficacy and adverse events in the enrolled patients. And to explore the markers associated with Progression Free Survival (PFS) by using Olink technique to detect blood samples from patients. To provide a better screening of the benefit population and provide guidance for the treatment of HER-2 positive metastatic breast cancer. Methods: From December 2019 to July 2023, our previous clinical trial prospectively enrolls 27 patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. Pyrotinib (400 mg, po, qd) combined with albumin-bound paclitaxel (200 mg, ivdrip, d1, d8, q21d) was used as the first-line treatment regimen. Patients were evaluated for efficacy. Survival analysis was performed by using the Kaplan-Meier method. Blood samples were collected during treatment. We selected 21 blood samples from patients, and dynamically detected plasma protein changes by Olink technique. Differential protein analysis between groups according to hormone receptor status, trastuzumab primary/secondary resistance, and the presence of visceral metastases. And the proteins associated with PFS were analyzed. Results: Among the 27 patients whose efficacy had been evaluated, 7 patients were evaluated as CR, 18 patients as PR, and 2 patients as SD. The objective response rate was 92.6%, and the disease control rate was 100%. The median follow-up was 17.8 months and the median PFS has not yet been reached. Diarrhea is the most common adverse event. Grade 3 or higher adverse events include diarrhea, leukocytopenia, neutropenia, and hand-foot syndrome. The progression free survival was significantly worse in patients with visceral metastases (P=0.01). Results of Olink protein dynamic assay showed a significant downregulation of CEACAM5, TXLNA, PVRL4and ERBB2. Differential proteins between groups showed that there were no significant differential proteins between the hormone receptor-positive and negative groups at the baseline node, but 7 proteins were upregulated in the hormone receptor-positive group compared with the negative group at the progression node, with EMS-1, WIF-1, and hK14 being the most significant. Compared to primary resistance, trastuzumab secondary resistance appeared 4 proteins upregulated at the baseline node, with hK14 and CYR61 being the most significantly; and 33 proteins were upregulated at the progression node, with CYR61, CXL17, FURIN, and ABL1 being the most significantly. Patients with high expression of TLR3 and low expression of RET at the baseline node had longer PFS. Conclusions: This study demonstrates that pyrotinib in combination with albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and a manageable safety for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. PFS was shorter in patients with visceral metastases. TLR3 and RET were the proteins that significantly associated with PFS in patients. Citation Format: Huihui Li, Xiaochu Man, Sha Yin, Dongdong Zhou, Baoxuan Zhang, Shu Fang, Fangchao Zheng, Chao Li, Xinzhao Wang, Wei Huang, Linlin Wang, Qingqing He, Hui Fu, Yan Zhang, Changrui Liu, Lin Dong, Xianguang Zhao, Liang Xu, Xiao Sun, Bingjie Fan, Lihua Song, Zhengbo Zhou, Qiaorui Tan, Jinming Yu. Efficacy, safety and translational study of pyrotinib combined with albumin-bound paclitaxel as firstline treatment of HER-2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-07.

Abstract PO2-05-01: Famitinib, a multi-targeted receptor tyrosine kinase inhibitor, combined with dalpicilib and fulvestrant in advanced HR-positive and HER2-negative breast cancer

Abstract Background: CDK4/6 inhibitors combined with endocrinotherapy (ET) represent an essential part of the treatment for HR-positive and HER2-negative breast cancer (BC). However, the role of angiogenesis inhibitors, such as bevacizumab, in these patients (pts) is controversial. While it has been demonstrated to improve progression-free survival (PFS), it has failed to show a significant overall survival (OS) benefit in HER2-negative BC. Several preclinical studies have explored the combination of anti-angiogenesis multi-targeted receptor tyrosine kinase inhibitors (TKIs) and CDK4/6 inhibitors in other cancers, suggesting a synergistic effect. Our phase Ib/II trial (NCT05176080, ChiCTR2100053950) aims to evaluate the safety and efficacy of a novel anti-angiogenesis TKI famitinib (F) added to dalpiciclib (D) and ET in advanced HR-positive and HER2-negative BC. Here we report the results of Phase Ib. Methods: A 3+3 de-escalation design was used in this dose-exploring phase (phase Ib). Pts with HR-positive and HER2-negative BC, who had no more than two prior chemotherapies in the advanced setting, were enrolled and administered F (orally, at doses of 15 mg/d, 10 mg/d, or 15 mg qod), D (orally, at doses of 150, 125 or 100 mg/d, 21 days on and 7 days off) and fulvestrant (intramuscularly, at a fixed dose of 500 mg every four weeks) until progression, unaccepted toxicities, or withdrawal. The initial dose level (Level 1) was set as F 15 mg daily and D 150 mg/d. The primary endpoints were recommended phase 2 dose (RP2D) and safety. Results: From December 2021 to June 2022, 18 pts were enrolled, and 3, 6, 3, and 6 pts were assigned to Level 1 (F 15 mg + D 150 mg), Level 2 (F 10 mg + D 125 mg), Level 3 (F 15 mg qod + D 125 mg), and Level 4 (F 10 mg + D 100 mg), respectively. 14 (77.8%) pts had visceral metastasis, and 7 (38.9%) had prior systemic therapies in the advanced setting. 13 (72.2%) pts had received ET, and 11 (61.1%) were resistant to ET before enrolled. A total of 6 dose-limiting toxicities (DLTs) were observed, including 3 Grade 4 thrombopenia (2 in Level 1, 1 in Level 2) and 3 Grade 4 neutropenia (2 in Level 3, 1 in Level 4), 4 of which were serious adverse events (AEs). The most common (≥20%) treatment-related AEs of Grade 3 or above were neutropenia (100.0%), leukopenia (88.9%), thrombocytopenia (33.3%), anemia (27.8%), lymphopenia and hypertension (both 22.2%). No death was reported. Overall 10 pts (55.6%) achieved confirmed partial responses and 16 (88.9%) achieved clinical benefits. Confirmed objective response rates (ORRs), clinical benefit rates (CBRs), and DLTs in different dose levels were shown in Table 1. Considering the efficacy and safety profiles, Level 4 was selected as RP2D. Conclusion: The anti-angiogenesis multi-targeted receptor TKI famitinib combined with CDK4/6i and fulvestrant has shown antitumor effects in advanced HR-positive and HER2-negative BC, and no new safety signals were observed. Citation Format: Min Yan, Mengwei Zhang, Limin Niu, Huimin Lv, Zhenzhen Liu, Huiai Zeng, Shengnan Zhao, Huihui Sun, Jing Wang, Yajing Feng, Huajun Li. Famitinib, a multi-targeted receptor tyrosine kinase inhibitor, combined with dalpicilib and fulvestrant in advanced HR-positive and HER2-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-01.

Abstract PS11-01: Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients

Abstract BACKGROUND Historic data suggest that incidence of brain metastasis (BM) is relatively distributed over time in HER2-positive (HER2+) breast cancer (BC), occurs early in triple negative BC (TNBC), and occurs late in hormone receptor-positive (HR+) metastatic BC (mBC). However, the timing of BM relative to line of therapy has not been well described. We describe the prevalence per line of therapy and cumulative incidence of BM in a large real-world cohort of patients (pts) with mBC, by BC subtype and line of therapy. METHODS This analysis used data from the longitudinal US Flatiron Health de-identified database, which provides unstructured and structured electronic health record-derived data from &amp;gt;2.6 million pts with cancer in ~800 unique sites of care. Eligible pts had initiated a first line of treatment (index data) for mBC up to March 1, 2021, to allow for ≥2 years potential follow-up time. Baseline characteristics were assessed, and pts categorized by HER2 and HR status: 1) HR+, HER2+; 2) HR+, HER2–, 3) HR–, HER2+ and 4) TNBC (i.e., negative for HR and HER2). For the last two categories, HER2-low subsets were defined based on immunohistochemistry results (1+, 2+, or equivocal). Lines of therapy were derived using both treatment regimens and progression data. The primary outcome was the first diagnosis of BM. The prevalence of BM was evaluated by subtype, at the index date, and by the line of therapy. The cumulative incidence function (CIF) of BM was used to estimate the risk of BM in pts free of BM at the index date, and death was treated as a competing event. RESULTS Overall, 18075 pts were included (HR+, HER2+: 3062 pts [16.9%]; HR–, HER2+: 902 pts [5.0%]; HR+, HER2–: 12331 pts [68.2%] [HR+, HER2-low: 7062 (39.1%)]; TNBC: 1780 pts [9.8%] [HR–, HER2-low: 725 pts (4.0%)]). Median age at the index date was 64 years (interquartile range: 54, 73) and 10271pts (56.8%) had visceral metastasis. In total, 5951 pts (32.9%) had de novo disease, 12090 (66.9%) had recurrent disease, and 34 (0.2%) did not have available data for mBC type. The table shows the number of pts by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date. Of the included pts, 1306 (7.2%) had a BM at the index date; the CIF was run on the remaining 16973 pts. Overall, 2248 pts (13.2%) had an incident BM event during follow-up (HR+, HER2+: 578 events; HR–, HER2+: 237 events; HR+, HER2–: 1119 events [HR+, HER2-low: 619 events]; TNBC: 314 events [HR–, HER2-low: 124 events]), 9314 had a competing event, and 5411 were censored. By fourth-line therapy, the prevalence of BM was 26.1% in HR+, HER2+; 37.1% in HR–, HER2+; 24.7% in TNBC (HR–, HER2-low: 27.9%); but remained low at 7.2% in HR+, HER2– (HR+, HER2-low: 9.4%). The cumulative incidence of BM at 60 months was 23% in HR+, HER2+, 34% in HR–, HER2+, 10% in HR+, HER2–, and, 22% in TNBC. Overall, the HER2-low subsets had BM prevalence and cumulative incidence that were very close to those that were HER2–. CONCLUSIONS This large analysis of real-world data demonstrates that the prevalence of BM across pts with mBC differs by tumor subtype and by line of therapy. Conversely, HER2-low status may have limited impact. The cumulative incidence of BM was highest in the HR–, HER2+ and TNBC subgroups, and lowest in the HR+, HER2– subgroup; despite this, due to the high proportion of HER2–, HR+ mBC cases, the HR+, HER2– group represented the largest number of BM events. These data emphasize the need for clinical and biologic predictors of BM and for strategies to prevent their onset, and provide information on the impact of BM inclusion and exclusion criteria in clinical trials for pts with mBC. Number of patients by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date BM, brain metastasis; HR, hormone receptor, pts, patients; TNBC, triple negative breast cancer. Citation Format: Sarah Sammons, Jose Leone, Thibaut Sanglier, Peter Lambert, Filippo Montemurro, Raf Poppe, Eleonora Restuccia, Sara Tolaney, Nancy Lin. Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS11-01.

Abstract PO5-05-07: Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam

Abstract Background The cyclin-dependent kinases (CDK)4/6 inhibitors (CDK4/6i) palbociclib and ribociclib have been available in Viet Nam since 2021 for the treatment of hormone receptor-positive metastatic breast cancer (MBC). Data regarding CDK4/6i benefit in Vietnamese MBC are sparse. This study evaluated the impact of CDK4/6i in first-line HR+/HER2− MBC using real-world experience at Ho Chi Minh City Oncology Hospital. Methods A single-institution study analyzed retrospective data from 108 patients treated with palbiciclib or ribociclib with endocrine therapy in first-line in HR+/HER2– MBC patients at Ho Chi Minh city oncology hospital. Patient characteristics, PFS, treatment response, and toxicity profiles were analyzed. Results Baseline patients’ characteristics are detailed in Table 1.The median follow-up was 12.5 months (95% CI: 10.9-13.3). Best responses by the line of therapy are in Table 2. The median PFS has still not been reached. The PFS rates at 6, 12 and 18 months were 94.4%, 93.5% and 91.5%, respectively. Patients with bone-only metastasis have a better PFS than visceral metastasis (p = 0.059). Patients with recurrent disease had shorter PFS (p = 0.083) than those presenting with de novo metastasis. The most common reasons for toxicity were neutropenia (92.6%), anemia (35.2%), thrombopenia (22.2%) and the incidence of diarrhea was only 2,8%. None were related to QTc-prolongation Conclusion The real-world effectiveness and safety with CDK4/6 inhibitors in our institution HR+/HER2– MBC patients mimics that observed in the clinical trials. This finding supports the use of CDK4/6i in combination with endocrine therapy as standard of care for HR+/HER2- MBC in Viet Nam. The study also suggests the need for more study of under-represented minority populations. Further studies are ongoing to validate these findings incorporating additional cancer centers. Keywords: advanced/metastatic breast cancer, Asia, CDK4/6 inhibitors, real world Table 1. Patient Demographics and Baseline Disease Characteristics (N=108) Characteristics N (%) Age, y: Median 52 Stage Recurrent from earlier stage, stages 0–III 67 (62) De novo, newly diagnosed stage IV at enrolment 41 (38) DFI &amp;lt; 12 months 5 (4.6) 12-24 months 12 (11.1) &amp;gt; 24 months 51 (47.2) No. of metastatic sites 1 49 (45.4) 2 37 (34.3) ≥ 3 22 (20.4) Metastasis pattern Bone only 30 (27.8) Other 78 (72.2) CDK4/6i Palbociclib 35 (32.4) Ribociclib 73 (67.6) Partner ET AIs 94 (87) Fulvestrant 14 (13) Table 2. Best responses of therapy (N=108) Best responses (N,%) CR 2 (1.9) PR 29 (26.9) SD 67 (62.1) PD 10 (9.3) Total 108 (100) ORR 31 (28.8) CBR 76 (70.3) Table. Citation Format: Hoang-Quy Nguyen, Hong-Duc Phan-Thi, Thi-Hong-Van Le. Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-07.

Abstract PO1-04-04: Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial

Abstract Aim: The efficacy and safety of inetetamab in combination with pyrotinib and oral vinorelbine was investigated in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive metastatic breast cancer after progression on trastuzumab were recruited. Patients received combined treatment of inetetamab (loading dose of 8 mg/kg, subsequent doses 6 mg/kg, intravenously once every 3 weeks) plus pyrotinib (400 mg orally once daily) plus vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR) and safety. The study was retrospectively registered in ClinicalTrials.gov on March 23rd, 2023. The registration number is NCT05823623. Results: Between Jan 1, 2022, and Dec 31, 2022, thirty patients were screened and enrolled to this study. The patients’ median age at enrollment was 54 years, twelve patients (40.0%) had hormone receptor-positive disease and 23 patients (76.7%) had visceral metastasis. The median PFS was 8.63 months (95% confidence interval [CI] 4.15 to 13.12 months). ORR was 53.3% (16/30) and DCR reached 96.7% (29/30). The most common grade III/IV adverse events included leukopenia (5[16.7%]), neutropenia (4[13.3%]) and diarrhea (3[10%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusions: The combination regimen of inetetamab plus pyrotinib plus oral vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer. Citation Format: Xiang Huang, Nan Jin, Chunxiao Sun, Xueqi Yan, Fan Yang, Yan Liang, Wei Li, Yongmei Yin. Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-04.

Abstract PO4-04-02: Real-world first line use of trastuzumab biosimilar (HLX02), pertuzumab and chemotherapy for Chinese patients with HER2-positive metastatic breast cancer

Abstract Background: HLX02 (Zercepac®) is the first manufactured trastuzumab biosimilar in China. Its similar efficacy, safety, and immunogenicity compared with Herceptin was confirmed in phase III clinical trials in patients with HER2-positive advanced breast cancer. Nevertheless, the real-world evidence of HLX02 combined with pertuzumab and chemotherapy in HER2-positive advanced breast cancer in China is still warranted. Methods: In this real world observational study, patients with HER2-positive advanced breast cancer who received HLX02, pertuzuamb and chemotherapy as first line treatment at Beijing Cancer Hospital from April 2020 to April 2023 were retrospectively and prospectively included. The primary outcome was progression-free survival (PFS), and secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). Results: A total of 55 patients (including one male) were included in this study and analyzed. The median age was 57 (range: 49, 62) years. Nearly one-third of tumors were estrogen receptor-positive (n=20, 36.4%). Thirty patients (54.5%) had newly-diagnosed stage IV disease. Visceral metastasis was reported in 40 patients (72.7%), most commonly observed in liver (n=22, 40%) and lung (n=19, 34.5%). Seven patients received prior anti-HER2 therapy during (neo-) adjuvant therapy (n=7, 12.7%). Taxane was the most commonly administrated chemotherapy regimen (n=51, 92.7%), including 56.4% albumin-bound paclitaxel, 20% liposomal paclitaxel and 18.2% docetaxel. Objective response was observed in 44 patients, leading to an ORR of 80%, and the DCR achieved 100%. HLX02 and pertuzumab was continued as maintenance therapy in 50 patients (90.9%), among which 17 combined with endocrine therapy (30.9%) and 6 combined with oral chemotherapy (10.9%). With a median follow-up of 9.8 months (range: 0.6-38.2). Progressive disease (PD) occurred in 12 of 55 patients (21.8%) and no deaths occurred. The median PFS was 24.8 months (95% confidence interval [CI]: 16.9- not estimated). The 12-month and 18-month PFS rate was 84.0% (95%CI: 72.9-96.9) and 58.8% (95%CI: 41.5 ~ 83.2), respectively. OS cannot be estimated yet due to immature data. HLX02-related diarrhea and infusion-related reaction was reported in 2 (3.6%) and 1 (1.8%) patients, respectively. LVEF values were monitored before and after drug administration, no clinical significant decline in LVEF and cardiac toxicity was observed. Conclusions: The trastuzumab biosimilar HLX02 demonstrated comparable efficacy and safety to Herceptin when combined with pertuzumab and chemotherapy for Chinese patients with HER2-positive advanced breast cancer in real world first-line treatment, which suggested that HLX02 may provide another option of Her2-targeted therapy combined with pertuzumab for Chinese patients. The benefit regarding long-term survival need to be further verified. Table 1. Effectiveness Citation Format: Ruyan Zhang, Guohong Song, Xiaoran Liu, Hui-Ping Li. Real-world first line use of trastuzumab biosimilar (HLX02), pertuzumab and chemotherapy for Chinese patients with HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-02.

Abstract PO4-05-14: Gene expression in metastatic breast cancer – patterns and prognostic potential

Abstract Introduction Metastatic breast cancer (mBC) is the leading cause of breast cancer mortality. However, mBC has a considerable variance in prognosis and course of disease, reflecting a substantial biological heterogeneity. Despite this, there is a lack of prognostic biomarkers validated for mBC. New prognostic markers and improved understanding of the molecular variants of mBC could aid in prognostication and personalizing treatments, and lead to the discovery of novel drug targets. The primary objective of this study was to explore the prognostic value of gene expression (GEX) in the distant metastasis (DM) of mBC. Secondly, we aimed to identify molecular subtypes of mBC, and describe their biological niches. Methods We used a cohort of mBC patients enrolled in a prospective trial (NCT01322893) that includes tissue from primary tumor (PT) and matched lymph node metastasis (LNM) and/or DM (1). The inclusion criteria were diagnosed mBC with a life expectancy of &amp;gt;2 months, ECOG score of 0-2, and an age of &amp;gt;18 years. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissue. GEX data were acquired for n=123 PT, n=71 LNM, and n=74 DM using the NanoString Breast Cancer 360 assay, which comprises 758 genes and &amp;gt;30 GEX signatures. The relationships between GEX and the endpoints overall survival (OS) and progression-free survival (PFS) were assessed using cox proportional hazards regression with GEX as a continuous score. Multivariable cox regressions were adjusted for PAM50 of the DM, number of metastatic sites, visceral metastasis, ECOG, and age at mBC diagnosis. Visualization by heatmap and k-means clustering were used to identify GEX patterns. When clustering single genes, we included only the 100 genes with the highest standard deviation. Results In relation to PFS, we found prognostically unfavorable roles of DM GEX of the signatures for Treg cells (HR=1.3, p=0.02), cytotoxicity (HR=1.3, p=0.03), and p53 (HR=1.3, p=0.02). Further, our data indicate prognostically favorable value of DM GEX of ESR1 (HR=0.77, p=0.02), PGR (HR=0.65, p=0.002), FOXA1 (HR=0.76, p=0.02), and AR (HR=0.68, p=0.0006). The prognostic value of AR remained in multivariable analysis. In relation to OS the first 2 years after mBC prognosis, we found prognostically favorable value of DM GEX of B7H3 (HR=0.65, p=0.04), TGFB (HR=0.53, p=0.02) and the signatures for stroma (HR=0.7, p=0.05) and claudin-low (HR=0.61, p=0.02). Finally, our data suggests that the previously published PAM50MET panel performs well as a prognostic indicator, especially when considered on a continuous scale, for PFS (HR=1.3, p=0.0023) and OS (HR=1.3, p=0.003) (2). Based on the 100 most highly variable genes, we identified five stable tumor clusters with distinct GEX profiles, where some strongly associated with metastatic site. Using the same approach on the GEX signatures, we established four GEX profiles able to outperform PAM50 in identifying tumors with poor OS in this material. Conclusion In this study, we demonstrate prognostic value for GEX-based panels in DM samples. First, we find GEX signatures related to hormone responsiveness to be favorable, and genetic instability to be unfavorable for mBC prognosis. We also demonstrate AR to be an independent marker for better PFS. Further, we confirm the prognostic value of PAM50MET, a previously published panel with the advantage of including only PAM50 genes and clinical parameters. Finally, we identify new GEX profiles related to metastatic site and outcome. These results illuminate the biological differences between mBC in relation to outcome and metastatic site. Better understanding of the mBC GEX subtypes may open new venues for tailored treatment.

Abstract PO4-04-04: A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive Metastatic Breast Cancer

Abstract Background Inetetamab, a new human epidermal growth factor receptor 2 (HER2) targeted antibody to optimize the ADCC effect, has shown great effectiveness in treating HER2-positive metastatic breast cancer. Pyrotinib, another HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Here, we investigated the efficacy and safety of inetetamb combined with pyrotinib and vinorelbine as treatment or HER2-positive metastatic breast cancer. Methods From Jan 2020 to July 2023, 77 HER2-positive metastatic breast cancer patients received inetetamb combined with pyrotinib and vinorelbine were enrolled in this study. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles were reported. Results The patients’ median age at enrollment was 53 years, 35 patients (45.5%) had hormone receptor-positive disease and 54 patients (70.1%) had visceral metastasis. The median PFS was 10.03 months (95% confidence interval [CI] 6.66 to 13.41 months). ORR was 62.3% (48/77) and CBR reached 77.9% (60/77). The most common adverse event (AE) was diarrhea, occurring in 36 patients (46.8%). While the most common grade III/IV AEs included neutropenia (9[11.7%]), leukopenia (8[10.4%]) and diarrhea (5[6.5%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusion The combination regimen of inetetamab combined with pyrotinib and vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer. Citation Format: Yongmei Yin, Wei Li, Xiang Huang, Nan Jin, Xinyu Wu, Chunxiao Sun, Yijia Hua. A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-04.

Abstract PO4-06-05: The prognostic impact of age at diagnosis of metastatic breast cancer according to estrogen receptor status: a single-center, retrospective study

Abstract Background: Young age is associated with poor prognosis and aggressive biology in early breast cancer, especially in luminal subtypes. But the prognostic impact of age in metastatic breast cancer (MBC) is unclear. Also it is known that chemotherapy is more effective in estrogen receptor (ER)-negative tumors than in ER-positive tumors and young patients respond better to chemotherapy. The authors tried to evaluate the impact of age on disease outcome according to ER status. Methods: We collected individual patient data from January 2000 to December 2022 from the Ewha Womans University Mokdong Hospital. Total 419 ER-positive and 238 ER-negative patients who had been treated for MBC were included for analysis. We compared clinical characteristics and overall survival (OS) of patients among three age groups (&amp;lt; 35, 35 to 50 and &amp;gt;50 years) at MBC diagnosis in ER-positive and -negative tumors. Results: The proportion of patients aged &amp;lt; 35, 35-50 and &amp;gt; 50 years was 3.1%, 46.6% and 32.3% in ER-positive tumors, and 2.7%, 14.8% and 18.4% in ER-negative tumors. Although most characteristics of tumors according to age were comparable, bone metastasis was more common in patients aged 35-50 years than the other age groups in ER-positive (51.8% vs. 36.0% in &amp;gt;50 years, P=0.006) and time to first metastasis was shorter in younger patients in ER-negative tumors (72.2% between 6 and 24 months vs. 31.1% in patients &amp;gt;50 years, P=0.003). The median follow-up time was 65 months. Overall survival rate was not different according to age in ER-positive tumors (P=0.909). On the other hands, younger patients had a higher risk of death in ER-negative tumors (P=0.015). In multivariate analysis, young age at MBC diagnosis (&amp;lt; 35years) with short time to metastasis (6 to 24 months), visceral metastasis, triple negative breast cancer was correlated with poor overall survival in ER-negative tumors (P=0.014, HR 1.77). Conclusions: Young age at MBC diagnosis was associated with a higher risk of death in ER-negative tumors, not in ER-positive tumors. These observations may suggest that physicians should consider the impact of age at diagnosis of metastasis and time course of disease in evaluating survival potential and determining a treatment strategy in metastatic breast cancers. Citation Format: Joohyun Woo, Ahrong Ham, Sewon Lee, Ji Eun Lee, Soo Ji Hong, Haena Lee, Sungchan Gwark, Jun Woo Lee, Hyun Goo Kim, Jungmin Jo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. The prognostic impact of age at diagnosis of metastatic breast cancer according to estrogen receptor status: a single-center, retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-05.