Line Systemic Treatment Research Articles

Patterns of progression in oligometastatic hormone receptor positive breast cancer after first-line systemic treatment at the metastatic stage.

e13054 Background: In recent years, thanks to large, consecutive and retrospective series, knowledge of oligometastatic breast cancer (OMBC) has improved. However, the underlying pathophysiological mechanisms and patterns of progression of OMBC remain largely unknown. The aim of this study is to determine whether the limited capacity of OMBC to metastasize persisted in patients receiving first-line systemic treatment at the OMBC stage. To obtain a biologically homogeneous cohort, the analysis focused on hormone receptor positive (HR+) OMBC. Methods: We retrospectively reviewed all patients consecutively diagnosed and treated from 2012 to 2020 at our institution for synchronous and metachronous HR+ OMBC. Included were HR+ MBC patients with up to five metastases at diagnosis with no other criteria. Clinical and biological characteristics at diagnosis of first metastases, types of treatment (local ablative treatment of all sites (LAT) vs palliative treatment), outcomes and patterns of progression after a first line systemic treatment at the oligometastatic stage were recorded. Progression-free survival (PFS) and overall survival (OS) rates with a 95% confidence interval were estimated using the Kaplan Meier method. Results: Out of 1,686 patients treated for MBC at our institution between 2012 and 2020, 11.0% (186/1,686) met inclusion criteria. Among these 186 HR+ OMBC patients, 62.2% had SBR grade I/II HR+, and 19.3% had HER2+ OMBC. 93.5% patients had only one organ invaded, and 88.2% patients had one to three metastases at diagnosis. 66.7% had bone metastases, 60.2% had bone-only metastases, 18.3% had visceral (lung or liver) metastases, 14.5% had lymph node metastases and 6.5% had brain metastases. 35.5% of patients were treated with a curative intent including systemic treatment plus LAT. After a median follow-up of 73.4 months (95%CI= [69.3-76.8]), median PFS and OS were respectively 31.6 months (95%CI= [23.7-37.4]) and 90.9 months (95%CI= [70.0-109.9]). Five years PFS and OS were respectively 32.6 % (95%CI= [25.5-39.9]) and 66.3% (95%CI= [58.4-73.1]). During this period, 64.0% (119/186) of HR+ OMBC patients presented disease progression. Among the latter, 74.1% showed spread with no more than five metastases (oligoprogression), and 82.6% in only one organ. 27.7% (33/119) of patients were able to benefit from LAT. Conclusions: HR+ OMBC incidence is 11%. Among patients with progressive HR+ OMBC following first-line systemic treatment at the oligometastatic stage, a large majority presented oligoprogression and a substantial proportion were able to be treated by local ablative therapy with a curative intent at the time of this progression. The limited capacity of HR+ OMBC to metastasize thus persisted after a first-line systemic treatment. This could be an argument in favor of physiopathological mechanisms specific to oligometastatic disease.

A retrospective study of tislelizumab combined with bevacizumab, pemetrexed, and carboplatin in driver-gene mutated advanced non-squamous non-small cell lung cancer after tyrosine kinase inhibitors failure.

e20620 Background: Overcoming resistance to tumor targeted therapies is a major challenge in the management of driver-gene mutated non-small cell lung cancer (NSCLC). Recent clinical trials suggested that the combination approach of immunotherapy, bevacizumab and platinum-based chemotherapy was effective for driver-gene mutated NSCLC after tyrosine kinase inhibitors (TKIs) failure. Our retrospective study was aimed to examine the efficacy and safety of tislelizumab (TIS) combined with bevacizumab plus chemotherapy for advanced driver-gene mutated non-squamous NSCLC (nsq NSCLC) who had failed to TKIs therapies. Methods: We retrospectively collected medical records of driver-gene mutations advanced nsq NSCLC who had failed to TKIs therapies in the Affiliated Hospital of Zunyi Medical University and Second Affiliated Hospital of Zunyi Medical University from January 2021 to December 2023. The participants were sorted into two groups. Pts in TBCP group received TIS combined with bevacizumab, carboplatin and pemetrexed (BCP) for six cycles, followed by TIS with pemetrexed as maintenance therapy. Pts in BCP group received BCP regimen for six cycles, followed by pemetrexed as maintenance therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 12 pts were enrolled (6 pts in TBCP group and 6 pts in BCP group). In TBCP group, there was one patient with EGFR exon 19del, KRAS, BRAF V600 mutation and RET fusion, respectively. 2 pts harbored EGFR exon 21 L858R mutations. In BCP group, 4 pts harbored EGFR exon 19del, 1 patient with exon 21 L858R, and 1 patinet with BRAF V600 mutation. All pts were failed to previous TKI therapy. 3 pts (50%) had progression after two systemic treatment lines in ABCP group. 4 pts(66.7%) had progressive disease after at least two systemic regimen. As of 6 February 2024 (median follow-up, 18.6 months), significantly longer PFS was observed in TBCP group compared with BCP group (HR = 0.269 [95% CI: 0.068-1.065], p = 0.0080). Median PFS was 14.20 months (95% CI: 0.5010-5.379) and 8.65 months (95% CI: 0.1859-1.996) in TBCP group and BCP group, respectively. A higher ORR assessed was observed with TBCP group (66.7%) compared with BCP group (33.3%). The DCR were both 100% in two groups. Median OS was not reached. Grade 3-4 TRAEs occurred in 1 and 2 pts in TBCP group and BCP group, respectively. Conclusions: TIS combined with bevacizumab, carboplatin and pemetrexed has shown a promising anti-tumor efficacy with manageable safety profile for TKI failure driver-gene mutations advanced nsq NSCLC. However, these findings still need to be further confirmed by prospective clinical trials with larger sample sizes.

Outcomes of patients with metastatic solid cancers treated on early phase clinical trials in western Australia.

e23094 Background: Cancer drug development is flourishing with novel immunotherapy combinations, antibody drug conjugates and increasingly molecularly targeted therapies that have pushed the inclusion of phase I clinical trials into earlier lines of systemic treatment. Linear Clinical Research is a dedicated Phase I centre with a catchment area of over 3 million people. We conducted a retrospective review into the outcomes of our centre. Methods: We included patients between 01/01/2020 to 30/04/2023, with advanced/metastatic or rare cancers with no available or suitable standard of care treatment. Data were extracted from our internal database with minimum follow up of 6 months. The primary endpoint was overall survival (OS). Other endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), duration of treatment (DOT), post-treatment survival (PTS), and 90-day mortality. Subgroup analyses based on treatment type were performed. Multivariate cox regression analysis was performed as part of tertiary endpoints. Results: 251 patients were recruited to 53 trials. Median age : 61 years (range: 21-83 years), 54.6% female, 74.1% Caucasian, ECOG 0-1: 90.8%, 26.7% rare cancers, 52.2% had 0-1 line of previous treatment, 47.8% had ≥ 2 lines. Trial treatments were: 51.4% immunotherapy (IO), 30.7% targeted therapy matched to molecular findings (TT), 2.8% antibody drug conjugate (ADC), 12.7% combination therapy (IO/TT/ADC/chemotherapy), 2.0% endocrine therapy alone, and < 1% chemotherapy. At data cut-off, 129 OS events had occurred (56.0%, median follow up of 22.0 months).The median OS was 16.0 months (95% CI 11.1 - 20.9), median PFS: 3.0 months (95% CI 2.2 - 3.8), ORR: 23.6%, DCR: 67.3%, median TTR: 2.0 months (IQR: 1.0-3.0), median DOR: 14.0 months (IQR: 6.0-38.0), median DOT: 3.0 months (IQR 1.0-10.0), median PTS: 7.0 months (IQR 2.0-27.0), 90-day mortality: 17.7%. Median OS based on treatment type: 11.0 months (95% CI 5.7-16.3) (IO), 12.0 months (95% CI 1.6-22.4) (TT), median not reached (range :1.0-28.0) (ADC), and 19.0 months (95% CI 13.6-24.4) (combination therapy). Median PFS based on treatment type: 2.0 months (95% CI 1.2-2.8) (IO), 5.0 months (95% CI 2.5-7.5) (TT), 10.0 months (95% CI: 0.0-28.0) (ADC), 6.0 months (95% CI 2.2 - 9.8) (combination therapy). Multivariate Cox analysis showed that higher number of lines of previous treatment was negatively associated with PFS and OS when adjusted for age, gender, type of treatment, and baseline sum of diameter (SOD). Conclusions: Our overall OS, ORR, and DCR are better than historical data of phase 1 during chemotherapy era , and are comparable to other centers nationally and internationally. Further work needs to be done to improve survival outcomes including algorithms to better match patients and trials earlier in their disease course.

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial.

10002 Background: Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved in the US for adult patients (pts) with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations, as determined by an FDA-approved companion diagnostic test, whose disease has progressed on or after ≥1 line of prior systemic therapy. Primary analysis of the RAGNAR study Broad Panel Cohort demonstrated tumor agnostic efficacy in pts with solid tumors harboring predefined FGFR mutations or fusions (Pant 2023). Here we report on Final Analysis of efficacy and safety results from the Pediatric Cohort of the RAGNAR study. Methods: Pediatric pts ≥6 years with advanced solid tumors and any FGFR mutation, fusion, or tandem duplication received oral erdafitinib. Starting doses were 8 mg, 5 mg, and 3 mg daily for ages > 15 years, 12 to < 15 years, and 6 to < 12 years, respectively, in 21-day cycles with possible individualized up-titration based on serum phosphate and adverse events (AEs). The primary endpoint was objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 or Response Assessment in Neuro-Oncology [RANO]) by independent review committee (IRC). Secondary endpoints included ORR by investigator, duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Results: 11 pts (median age 13 years; range, 6-16; 64% female) received erdafitinib. Median follow-up was 9.7 months at data cutoff. Histologies included low-grade glioma (LGG-6 pts); high-grade glioma (HGG-3 pts); soft tissue sarcoma (1 pt), and temporal neurocytoma (TNEURO-1 pt). 7, 1, and 3 pts had FGFR1, FGFR2, and FGFR3 alterations, respectively. 6, 4, and 1 pts had FGFR fusions, mutations, and tandem duplication, respectively. Pts had a median of 1 prior line of systemic treatment; 6 (55%) had prior radiotherapy. At data cutoff, 1 of 3 pts (33%) with HGG and an FGFR1-TACC1 fusion achieved a partial response based on investigator assessment with a response duration of 19.8 months. Investigator-assessed objective responses were not observed in the other tumor types. DCR and CBR were 100% in pts with LGG and 67% in pts with HGG. Most common treatment-emergent adverse events (TEAEs) included hyperphosphatemia (64%), diarrhea (64%), pain in extremity (45%), alanine transaminase increased (36%), nausea (36%), and onycholysis (27%). No central serous retinopathy events occurred; related serious adverse events (SAEs) occurred in 4 (36%) pts, including 1 SAE of epiphysiolysis; there were no related TEAEs leading to death. Conclusions: In this small pediatric population comprising primarily refractory HGG and LGG with any FGFR alteration, erdafitinib demonstrated limited objective responses but promising disease control with acceptable safety. Clinical trial information: NCT04083976 .

Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multicenter, open-label, single-arm, phase II study.

e13139 Background: The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 14 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 70 patients were enrolled from November 2021 to October 2023; 47 (71.4%) had HR+HER2- and 18 (28.6%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (68.6%), liver (52.9%), lymph nodes (48.6%), lung (44.3%) and brain (10.0%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 48.6%, the DCR was 92.9% and the median PFS was 7.2 months. For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 6.3 months. Among HR+ patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of HR+ patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. For the HR+ HER2-low subgroup, the median PFS was 8.4 months. The most common grade 3-4 AEs were hematological, including neutropenia (38.6%), leukopenia (31.4%), anemia (24.3%), and thrombocytopenia (15.7%). Grade ≥3 perceived AEs were relatively low. Conclusions: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]

Adverse events of patients treated with antibody-drug conjugates in phase 1 clinical trials at the Royal Marsden Drug Development Unit from 2014 to 2024.

e15020 Background: Antibody-drug conjugates (ADCs) are designed to improve therapeutic indices of cytotoxic agents. Nevertheless, they may induce unexpected toxicities not observed with parent payloads. This study aimed to characterize the adverse events (AEs) seen in patients treated with ADCs in Phase 1 trials at The Royal Marsden Drug Development Unit (DDU). Methods: This is a retrospective cohort analysis of consecutive patients who received at least one dose of an ADC in a phase I trial from January 2014 to January 2024 at The Royal Marsden DDU. Descriptive statistics of patient characteristics, ADCs, and treatment-related AEs were performed. Univariate and multivariate logistic regression will be utilized to assess correlations among patient and ADC characteristics and adverse events. P values of < 0.05 will be considered significant. Results: A total of 131 patients who participated in twelve ADC trials were included. The median age of participants was 63 years (range: 31-84) and 61% were females. Patients received a median of three prior lines of systemic treatment. The most common type of ADC target, antibody, linker and payload were receptor tyrosine kinase (51%), humanized IgG monoclonal antibody (69%), valine-citrulline (VC) cleavable linker (85%), and a tubulin-binding payload (59%), respectively. Most patients received an ADC dose of 1-3 mg/kg (76%) with each cycle given once every 3 weeks (64%). The median number of cycles was 3 with an average treatment duration of 63 days. Within the cohort, 89% of patients developed any grade AE and 17% experienced grade 3 or higher AEs. The major treatment-related AEs were fatigue (48%), nausea/vomiting (27%), ocular toxicity (26%), neuropathy (26%), skin rash (20%) and pneumonitis (8%). The median time to first onset of treatment-related adverse events were 37 days for ocular toxicity, 46 days for pneumonitis, and 54 days for neuropathy. ADC-related AEs led to treatment interruptions (51%), dose reductions (13%), and treatment discontinuations (28%). Two treatment-related grade 5 events occurred. The objective response rate was 18%, with 1 complete response and 22 partial responses. Conclusions: Despite being designed to minimize side effects, ADCs were associated with significant toxicities, including unexpected adverse events unrelated to target, antibodies or the payloads, limiting their therapeutic indices. Further analysis of the relationship between different components of the wide range of ADCs and AEs are warranted to better understand the potential mechanisms of ADC toxicity.

A first-in-human study of CRISPR/Cas9-engineered tumor infiltrating lymphocytes (TILs) product GT316 as monotherapy in advanced solid tumors.

2549 Background: A next-generation TIL product GT316 was engineered with CRISPR/Cas9 to genetically disrupt two key immunoregulatory targets identified from a genome-wide CRISPR screening platform and demonstrated significantly enhanced anti-tumor efficacy and persistence in pre-clinical animal studies with ameliorated TIL exhaustion profile. A first-in-human trial was initiated to evaluate the preliminary safety and efficacy of GT316 in advanced solid tumors. Methods: The first-in-class study is to enroll patients (pts) with advanced treatment-refractory solid tumors, especially gynecological tumors. Once the optimal biological dose (OBD) is identified, a monotherapy expansion phase will be initiated for pts with various solid tumors. Enrolled pts were preconditioned with a nonmyeloablative (NMA) lymphodepletion regimen and treated by infusion of the GMP-grade G316 product followed by IL-2 administration. Results: As of January 22, 2024, the dose escalation study enrolled 4 pts, all of whom were female with a median age of 58 years with 1 to 9 prior lines of systemic treatment. The median number of infused TIL cells was 1.0E+10. All pts experienced TRAEs with the majority being grade 1 or 2. Grade 3/4 TRAEs included lymphocyte count decreased, white blood cell count decreased, monocyte count decreased and neutrophil count decreased, which were related to the NMA regimen. No dose-limiting toxicities (DLTs) or TIL-related grade≥3 TRAEs were observed. Median time on study was 33.4 wks (8–35 wks). One pt with treatment-refractory cervical cancer experienced a confirmed complete response (CR) after 4 wks and the duration of response is 32 wks by now (RECIST 1.1). One ovarian cancer pt with 9 lines of previous systemic therapies experienced a confirmed partial response (PR) after 4 wks and the duration of response is 22 wks by now (RECIST 1.1). Response data will be continuously collected. The other two ovarian cancer pts experienced stable disease (SD) and progressive disease (PD), respectively. Despite varying doses of TILs (3.2E+09 to 1.90E+10) and IL-2 (up to 3.0E+05 IU/kg), all pts receiving GT316 showed robust TIL expansion post-infusion, which is positively correlated with administrated IL-2 doses. Enhanced IFN-γ secretion could be detected in the serum of the CR and PR pts compared to the SD and PD pts, indicating potential tumor antigen-specific response. Conclusions: The first-in-human study of GT316, a CRISPR/Cas9-dual KO anti-exhaustion TIL product, demonstrates good tolerability with encouraging preliminary anti-tumor efficacy as a monotherapy in pts with advanced solid cancers. The infusion of GT316 was associated with robust TIL expansion and IFN-γ secretion. Updated data with additional follow-up will be continuously collected, and OBD will be determined based on the overall data of safety and preliminary efficiency. Clinical trial information: NCT06145802 .

Changing treatment patterns for hepatocellular carcinoma: A SEER-Medicare study.

e16166 Background: Sorafenib was the first systemic therapy approved in 2005 for hepatocellular carcinoma (HCC), then 9 new therapies were approved between 2017-2022. No studies have evaluated treatment patterns of systemic therapy since these therapies became available. Methods: This retrospective cohort study used SEER-Medicare data to identify patients with a new diagnosis of HCC between 2014-2019 and associated comorbidity and treatment claims through 2020. Patients had continuous coverage with Medicare Parts A/B/D from 3 months before diagnosis to the earlier of 3 years, death or censoring. We excluded deaths reported by death certificate or autopsy. We used claims to identify receipt of local therapies (ablation, transplant, resection, transarterial bland/chemo/radioembolization, external/stereotactic radiation, brachytherapy) and all FDA-approved systemic therapies for HCC. We described cohort characteristics, treatment patterns, and overall survival (OS) and used Chi-squared statistics to compare treatment patterns and OS for patients diagnosed between 2014-17 vs 2018-19. Results: 11,799 patients were included (69.2% male, 76.9% White, median age: 71 years, 36.2% NAFLD, 44.1% Hepatitis C, 10.6% Hepatitis B, 28.1% alcoholic liver disease). Within one year of diagnosis, 76.3% of all patients received any local or systemic treatment, which did not change over time (2014-17: 76.1%, 2018-19: 76.6%, p=0.60). Receipt of local therapy within 1 year was unchanged (2014-17: 73%, 2018-19: 73.2%, p=0.77) and there were no clinically significant changes in treatment rates for specific local therapies. Receipt of systemic therapy in the first year decreased slightly (2014-17: 16.97%, 2018-19: 15.2%, p=0.012). First line systemic treatment changed drastically: 83.7% of patients diagnosed in 2014-17 received first-line sorafenib vs only 40.1% of those diagnosed 2018-19 (Table). Median overall survival for patients receiving no treatment, systemic therapies first or local therapies first was 1.9, 11 and 16.3 months, respectively. Among patients receiving systemic therapy first, survival from initiation of first line treatment increased from 9.1 to 11.2 months for patients diagnosed in 2014-17 vs 2018-19 (p= <.0001). Conclusions: While overall local and systemic treatment rates have not changed substantially, more recent patients with HCC are more likely to receive first-line novel therapies over first-line sorafenib and associated survival has modestly increased. [Table: see text]

Cisplatin monotherapy as a treatment option for patients with HER-2–negative breast cancer facing hepatic visceral crisis or impending visceral crisis: A single-center cohort study.

e13057 Background: The international consensus guidelines, ESO-ESMO's fifth edition, characterize visceral crisis (VC) in advanced breast cancer (ABC) as a swift rise in bilirubin during disease progression. The guidelines also briefly address the impending VC (IVC) definition. Systemic treatment data for hepatic VC/IVC are scarce and lacking in international guidelines regarding BC treatment. This study explores cisplatin monotherapy's safety and efficacy in HER2-negative BC patients with hepatic IVC/VC. Methods: In this retrospective cohort study conducted at a Reference Cancer Center in Southern Poland, data from HER2 negative ABC patients who underwent cisplatin monotherapy (60-80mg/m2, every 3-4 weeks) between 2016 and 2023 were examined. Hepatic VC followed ABC5 definition of rapid bilirubin elevation >1.5 times the upper limit of normal (ULN) due to diffuse liver metastases, in the absence of biliary tract obstruction or Gilbert's syndrome; IVC was characterized by rapid, symptomatic liver progression, a majority of liver involvement, with ALT or AST >2 x ULN, and significant increases in LDH, alkaline phosphatase, or GGTP. Results: The study included 33 female participants (24 hormonal positive) with a mean age of 53.8 years (range 34-77). Among them, 10 were identified with hepatic VC, and 23 with IVC. Median number of previous palliative systemic treatment lines was 2 (range: 0-5). The median progression-free survival was 1.87 months and the median overall survival was 2.67 months. Patients received median 1 cycle of cisplatin (1-6): 17 patients received only one cycle, 6 patients two cycles and 10 patients ≥three cycles. Using the Conditional Inference Trees algorithm allowed to assess that patients with performance status (PS) 0 or 1 (15 patients) had a 66.67% chance of achieving stable disease (SD) or partial regression (PR) as the best response, while patients with PS ≥2 (18 patients) had a 5.6% chance of achieving SD or PR as per Response Evaluation in Solid Tumors 1.1 Criteria (median time from cisplatin initiation to imaging studies 2.23 months). Eight patients experienced adverse events of grade ≥3, such as fatigue or nephrotoxicity leading to dose reduction in 5 cases and treatment discontinuation in 2. Conclusions: The differentiation between IVC and VC lacks precision. Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are lacking. Our study explored cisplatin's potential use, finding it to be a feasible choice in patients with PS ≤1 experiencing hepatic IVC/VC, regardless of liver function parameters. Almost one-third of our patients were administered treatment in the last 30 days of life, potentially adversely affecting their quality of life and causing unwarranted suffering and costs. Academic clinical trials should be organized to address this pressing medical gap.

Abstract PO5-04-14: Quality of Life (QoL) among metastatic hormone receptor positive, HER2 negative breast cancer patients during first line systemic treatment

Abstract Background Current international guidelines recommend endocrine therapy combined with a CDK4/6 inhibitor as the preferred first line systemic treatment in patients diagnosed with metastatic hormone receptor positive (HR), HER2 negative breast cancer (BC). Randomized controlled trials that led to the approval of these agents in the first line disease setting are derived from controlled environments and selected patients. We aimed to assess real-world patients’ characteristics, safety and health related quality of life in a non-select cohort of patients being managed in a Brazilian private Cancer Center. Methods: We performed a cross sectional study at Beneficencia Portuguesa de Sao Paulo evaluating quality of life among patients with metastatic HR+/HER2 negative treated in the first line disease setting. Inclusion criteria included patients that received the combination of a CDK4/6i with any endocrine therapy (ET) between January 2018 and April 2023. Primary endpoint was quality of life assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ-BR23, it is baseline, there is only one measurement for each patient. Results: We analyzed 72 patients who meet the inclusion criteria. Median age at diagnosis was 49 years old (ranging from 31 to 91). Approximately half of the population was premenopausal (51%). Palbociclib and abemaciclib were the most commonly used CDK4/6i, with 42 and 35% of patients, respectively. ECOG performance status was zero or one in almost the entire patient population analyzed (97%). 53% of the patients were diagnosed as de novo metastatic BC. Table 1 and 2 summarize the patients characteristics. Mean global health status was 75.4, with social and cognitive functioning scoring the highest (Mean 78.6 and 79.1, respectively). The most distressing symptom among the symptom scale was fatigue (Mean 27.2). Most symptoms and functioning scales did not meet the threshold for clinically meaningful differences between the different CDK4/6 inhibitors. Conclusion: Real-world data from our study is consistent with the historical expected health related quality of life among patients diagnosed with HR+/HER2 negative metastatic BC in the first line disease setting. Table. Citation Format: Débora Gagliato, Julio Antonio Araujo, Bianca Milena Verboski, Guilherme William Marcelino, Fabiana Nogueira Momberg, Gilmara Silveira da Silva, Rozana Mesquita Ciconelli, Antônio Buzaid. Quality of Life (QoL) among metastatic hormone receptor positive, HER2 negative breast cancer patients during first line systemic treatment [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 PO5-04-14.

Abstract PO3-05-01: Locoregional Management Based on Mode of Progression for HR+/HER2- metastatic breast cancer Treated with Combined CDK4/6 inhibitor with Aromatase inhibitor

Abstract Background - Standard management for HR+/HER2- metastatic breast cancer (MBC) comprises concurrent aromatase inhibitor (AI) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), providing improved progression-free (PFS) and overall survival over anti-estrogen alone. Eventual resistance mechanisms potentially include phenotypic changes, clonal selection, and new mutations. We theorized that limited progressive disease (LPD) would be more common on combination therapy due to eventual new mutations or clonal selection, in comparison to generalized progressive disease (GPD) occurring more frequently on AI alone due to phenotypic cellular changes across all disease sites. Potentially loco-regional treatment (LRT) options could significantly extend disease control in selected patients on combined therapy. Methods - Patterns of progressive disease (PD) for 55 historical AI-only treated controls (group A) were compared to those for 60 patients on combined treatment with an AI and a CDK4/6 inhibitor (group B) for first-line management of HR+/HER2- MBC. Mode of progression was classified as general (GPD - PD in the majority of lesions) or limited (LPD - PD in up to three lesions in a single organ). All LPDs were assessed for suitability for LRT at time of progression. PFS was assessed for those with LPD who continued present treatment after locoregional therapy. Results - LPD occurred in 13 of 55 patients (23.6%) in group A compared to 26 of 60 (43%) in group B (p = 0.026). For LPD patients, all 13 cases in group A were considered appropriate for LRT but only 3 (23.1%) received it and all patients also switched systemic therapy. In group B, 23 of 26 LPD patients were considered suitable for LRT and 16 (57.7%) received it, of whom 11 then continued first line systemic treatment. For these 11 group B patients median PFS was 12+ months (range 3 to 36+ months). LRT consisted of RT in 14 cases (bone in 13 cases, lymph node in one case) and resection in one (isolated brain metastasis). Conclusion - Patients treated with combined CDK4/6i and AI for first line HR+/HER- MBC were significantly more likely to develop LPD than those on single agent anti-estrogen, where local therapy could often be delivered with no change to systemic therapy. This strategy, applied to 11 of 60 combination treated patients (18%), delivered a median PFS in excess of a year. In contrast more general PD was more commonly observed in patients treated with AI alone, warranting change in systemic therapy. Citation Format: Andrew Redfern, Ngie Law, Indunil Weerasena, Lisa Spalding, Hilary Martin. Locoregional Management Based on Mode of Progression for HR+/HER2- metastatic breast cancer Treated with Combined CDK4/6 inhibitor with Aromatase inhibitor [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 PO3-05-01.

Abstract PO3-05-10: Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II study

Abstract Background: Eribulin is a halichondrin non-taxane inhibitor of microtubule dynamics approved in China for advanced breast cancer patients who have received at least two prior chemotherapy treatments. The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 13 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 65 patients were enrolled from November 2021 to May 2023; 47 (72.3%) had HR+/HER2- and 18 (27.7%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (70.8%), liver (58.5%), lymph nodes (50.8%), lung (43.1%) and brain (10.8%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 52.3%, the DCR was 92.3% and the median PFS was 7.6 months (Table). For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 7.6 months. Among patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. The most common grade 3-4 AEs were hematological, including neutropenia (41.6%), leukopenia (33.9%), anemia (23.1%), and thrombocytopenia (15.4%). No grade ≥3 perceived AEs were reported. Conclusion: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Table. Summary of efficacy outcomes Citation Format: PeiJian Peng, Xiao-Lu Xu, Jin-Cai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, Cai-Wen Du, Guorong Zou, Jie Ouyang, Ying-Ying Shi, Fei Xu, Geng-Sheng Yu, Yong-Kui Lu, Yong-Xia Wang, Shi-En Cui, Lu-Zhen Li. Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II 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 PO3-05-10.

Abstract PO3-15-05: B cell immunology predict response and survival in PD-1/PD-L1 targeting immune checkpoint inhibition of metastatic breast cancer

Abstract Critically understudied in the era of T cell immunotherapies, aggregation of B cells within tertiary lymphoid structures (TLS) has recently been linked to improved response and survival in immune checkpoint inhibition (ICI). While this has been reported for several cancers, including melanoma, lung cancer, bladder and renal cell cancer, there is an unmet need to understand molecular patterns in tumors with limited mutational burden (TMB) and low overall abundance of tumor infiltrating lymphocytes (TILs). Here, we report on the landscape of B cells in metastatic breast cancer, inferred by bulk sequencing (WGS/RNAseq) and multiplexed ion beam imaging (MIBI-TOF) in 203 patients across the breast cancer biology (ER/PR/HER2), collected from real world data (CATCH diagnostic and register study, NCT05652569). Median age was 53 years (range, 23-79), with a median of 3 systemic treatment lines for advanced or metastatic disease. The majority of biopsies were taken from the liver (49%), followed by breast (15%), lymph node (13%), skin (6%) and lung (6%). Immunohistochemistry based subtyping revealed 61% of the HR+/HER2- (or Luminal HER2-), followed by 26% of HR-/HER2- (TNBC), and 15% of HER2+ subtype. Immunological subtyping by stromal TILs and CD8+ infiltrates defined 3 subgroups with 57% being desert, 18% inflamed and 19% of no special type (6% NA). The majority (52%) was scored CD20+ with minimal colocalization in 45% of samples. MIBI-TOF demonstrated a continuum of coordinated B cell and T cell aggregation in the tumor microenvironment with lymphoid aggregates in 29% and mature TLS structures in 26% of patients. No correlation with conventional biomarkers for immunogenicity (PD-L1, TMB) has been observed. Chart review identified 21 patients treated by immune checkpoint blockade (ICI) targeting PD-1 (Pembrolizumab) or PD-L1 (Atezolizumab), either as monotherapy or in combination with chemotherapy/targeted therapy. Overall response rate (ORR) at week 12 was 57%, disease control rate (DCR) was 71%. RNA signature levels for germinal center signalling, B cell activation and antibody secretion correlated with quality of B cell aggregation and, importantly, significantly with response to ICI (Kruskal Wallis p=0,028). B cell derived prediction of response was independent of PD-L1 protein expression, breast cancer subtype, BRCA mutation status or TMB. Downstream single cell analysis, computational immunogenomics as well as spatial neighbourhoods will be reported at the meeting. These results extent B cell centered molecular insights to metastatic breast cancer and may pave the way for a composite biomarker, selecting patients for ICI who benefit meaningful and would not have been identified by the current standard of care. Citation Format: Carlo Fremd, Markus Schulze, Miray Cetin, Hannah Boehm, Bénédicte Lenoire, Oezlem Akilli-Oeztuerk, Inka Zörnig, Pornpimol Charoentong, Yanhong Lyu, Catch Collaborators, Daniel Hübschmann, Felix Kommoss, Verena Thewes, Andreas Schneeweiss, Marc Zapatka, Felix Hartmann, Peter Lichter. B cell immunology predict response and survival in PD-1/PD-L1 targeting immune checkpoint inhibition of 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 PO3-15-05.

Treatment sequencing and impact of number of treatment lines on survival in follicular lymphoma: A national population-based study.

Follicular lymphoma (FL) is a clinically heterogeneous disease. The need for treatment, treatment sequencing, number of treatment lines, and its association with survival have not been described in a population-based setting. We identified all patients diagnosed with FL in the Swedish Lymphoma register from 2007 to 2014, followed until 2020, with detailed data on progression/relapse, transformation, and 2nd and further lines of therapy. During a median follow-up of 6.8 years, 1226 patients (69%) received 1st systemic treatment, 358 patients (20%) were managed with watch-and-wait (WaW) only, and 188 (10%) patients were treated with radiotherapy and did not require additional therapy during the study period. Among patients starting systemic treatment, 496 (40%), 224 (18%), and 88 (7%) received 2nd-, 3rd-, or 4th-line therapy, respectively. The 10-year cause-specific cumulative incidence of transformation was 13%. Among patients managed with 1st line R-single, R-CHOP, or BR, 54%, 33%, and 29% required 2nd line, respectively. The cumulative probability of starting subsequent treatment within 2 years was 26% after 1st line and 35% after 2nd line treatment. Two-year OS following 1st, 2nd, 3rd, and 4th line systemic treatment was 84%, 70%, 52%, and 36%, respectively, and remained similar when excluding transformations. We conclude that a substantial proportion of FL patients can be managed with WaW for a long period of time, while patients who require multiple treatment lines constitute a group with a large clinical unmet need. These results constitute valuable real-world reference data for FL.

NGS-Guided Precision Oncology in Breast Cancer and Gynecological Tumors-A Retrospective Molecular Tumor Board Analysis.

Background: Precision oncology treatments are being applied more commonly in breast and gynecological oncology through the implementation of Molecular Tumor Boards (MTBs), but real-world clinical outcome data remain limited. Methods: A retrospective analysis was conducted in patients with breast cancer (BC) and gynecological malignancies referred to our center's MTB from 2018 to 2023. The analysis covered patient characteristics, next-generation sequencing (NGS) results, MTB recommendations, therapy received, and clinical outcomes. Results: Sixty-three patients (77.8%) had metastatic disease, and forty-four patients (54.3%) had previously undergone three or more lines of systemic treatment. Personalized treatment recommendations were provided to 50 patients (63.3%), while 29 (36.7%) had no actionable target. Ultimately, 23 patients (29.1%) underwent molecular-matched treatment (MMT). Commonly altered genes in patients with pan-gyn tumors (BC and gynecological malignancies) included TP53 (n = 42/81, 51.9%), PIK3CA (n = 18/81, 22.2%), BRCA1/2 (n = 10/81, 12.3%), and ARID1A (n = 9/81, 11.1%). Patients treated with MMT showed significantly prolonged progression-free survival (median PFS 5.5 vs. 3.5 months, p = 0.0014). Of all patients who underwent molecular profiling, 13.6% experienced a major clinical benefit (PFSr ≥ 1.3 and PR/SD ≥ 6 months) through precision oncology. Conclusions: NGS-guided precision oncology demonstrated improved clinical outcomes in a subgroup of patients with gynecological and breast cancers.

Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB). In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022. From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality. TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Metastasis-Directed Stereotactic Body Radiotherapy in Prostate Cancer Patients Treated with Systemic Therapy and Undergoing Oligoprogression: Report on 11 Consecutive Cases

Background: Stereotactic body radiotherapy (SBRT) targeted at metastatic sites of disease progression is emerging as a potential therapeutic approach for managing oligoprogressive prostate cancer. However, a definitive benefit has yet to be demonstrated. Herein, we present our institution’s experience with this treatment approach. Methods: From April 2018 to March 2023, 11 patients affected by oligoprogressive prostate cancer were treated with SBRT targeting the nodal or bone sites of progression while maintaining the ongoing systemic therapy. Three patients were undergoing single-agent ADT (Androgen Deprivation Therapy), while the remaining eight were receiving a subsequent line of systemic therapy. All patients were evaluated with a pre-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT, which demonstrated between one and five localizations of disease. All the active sites were treated with SBRT in one (15–24 Gy) or three (21–27 Gy) fractions, except for one patient, who was treated in five fractions (35 Gy). PSA serum levels were tested at baseline, one month after RT and at least every three months; all patients underwent a post-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. The evaluated endpoints were PSA response, defined as a post-treatment decrease &gt;50% from baseline measured within 6 months, time to next-line systemic treatment (NEST), local control (LC), biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS) and freedom from polymetastatic progression (FPP). Results: Nineteen lesions were treated (seven nodal and twelve bone). At a median follow-up of 19 months (7–63), 9 of the 11 patients had a PSA response; all patients had local control of the treated metastases. A total of six patients switched to a next-line systemic treatment, with a median NEST of 13 months. Six patients had polymetastatic progression with an FPP median time of 19 months. No patients died during the follow-up period. The SBRT-related toxicity was negligible. Conclusions: Our data support the use of SBRT targeting the sites of oligoprogressive disease before moving to a subsequent line of systemic treatment in patients with metastatic prostate cancer. Prospective studies to evaluate the potential impact of this approach on overall survival are warranted.

Abstract 2576: Radiomic features of intrathoracic lesions can predict the mixed response in non-small cell lung cancer treated with immunotherapy

Abstract Background: Although immunotherapy has emerged as a promising treatment for lung cancer, the decision to continue immunotherapy becomes challenging when mixed response (MR) occurs. This study is aimed to evaluate whether radiomic features from pre-treatment intrathoracic images can predict MR. Methods: 127 consecutive patients with NSCLC who received first line systemic treatment containing immunotherapy were included in this study. Chest CT scans were obtained at baseline and 1-3 times from 11 different CT scanners and harmonization method was applied to minimize scanner-related bias. The durable response of intrathoracic lesions (n=266) at least 24 weeks was evaluated based on RECIST 1.1 and irRECIST. MR was defined as the simultaneous presence of at least one lesion that increased and decreased in a single patient during immunotherapy and two different criteria of MR for the change of tumor lesions were applied: Definition-A (MR-A), Δ [baseline - first follow-up] ≥ 5 mm; Definition-B (MR-B), any change of Δ [baseline - first follow-up]. All intrathoracic lesions were identified and segmented by four different physicians. Radiomic features, including morphological, intensity, GLCM, GLRLM, GLSZM, and NGTDM, were extracted using LIFEX software (IMIV/CEA, Orsay, France). Confusion matrix was used to assess tumor responses, and area under the curve (AUC) for intrathoracic lesions was calculated. Results: Tumor responses based on irRECIST were CR (n=1, 0.8%), PR (n=33, 26.0%), SD (n=55, 43.3%), and PD (n=39, 30.7%). There were 10 cases (7.9%) of MR-A and 25 cases (19.7%) of MR-B. While the median progression-free survival (PFS) and overall survival (OS) in MR-A group were 22.9 (range, 0.5-50.6) and 23.5 (range, 1.1-42.2) months, those in MR-B group were 2.0 (range, 0.5-50.6) and 3.3 (range, 0.7-49.0) months respectively. While the overall sensitivity (SN) and specificity (SP) for MR-A in intrathoracic lesions were 0.55 and 0.87, those for MR-B were 0.52 and 0.71, respectively. The AUC for MR-A and MR-B were 0.71 and 0.62 respectively, and the AUC for durable response was 0.56. In the SD group, median PFS and OS were 3.3 (1.4-18.9) and 6.1 (4.8-26.2) in the MR-A group and 9.7 (0.7-18.9) and 23.9 (0.7-26.2) respectively in the MR-B group. Median PFS and OS were 18.2 (0.5-65.2) and 23.9 (0.9-55.3) respectively in the non-MR-A group and 18.2 (0.5-65.2) and 23.9 (0.9-55.3) respectively in the non-MR-B group. In the PD group, median PFS and OS were 23.5 (0.5-41.3) and 24.7 (1.1-42.2) respectively in the MR-A group and 5.1 (0.5-41.3) and 11.5 (1.1-49.0) respectively in the MR-B group. Median PFS and OS were 20.3 (0.7-71.4) and 37.1 (1.0-72.9) respectively in the non-MR-A group and 20.3 (0.7-71.4) and 37.1 (1.0-72.9) respectively in the non-MR-B group. Conclusion: The radiomic features in NSCLC patients who received immunotherapy may help predict MR in NSCLC patients treated with immunotherapy. Citation Format: Monica Yadav, Jeeyeon Lee, Peter Haseok Kim, Maria J. Chuchuca, Taegyu Um, Liam Il-Young Chung, Yury S. Velichko, Young Kwang Chae. Radiomic features of intrathoracic lesions can predict the mixed response in non-small cell lung cancer treated with immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2576.

Abstract 4627: Metastatic renal cell carcinoma with occult primary: Clinical and biological evidence for a new entity of cancers of unknown primary that beneficiates from tissue-tailored treatment

Abstract Background: Cancers of unknown primary (CUP) is a heterogenous group of malignancies characterized by distant metastases in the absence of detectable primary. Specifics subgroups of CUP that share similarities with cancers of known primary beneficiate from tissue-tailored therapeutic strategies. The objective of this study was to characterize the clinical and biological presentation of a cohort of patients with suspected CUP of renal origin (rCUP) and to evaluate their optimal therapeutic management. Methods: All Patients with rCUP identified prospectively between 2020 and 2023 within the French National Multidisciplinary Tumor Board for CUP were included. Centralized pathological review and immunohistochemical stainings were performed. Whole Exome Sequencing (WES), whole transcriptomic sequencing (RNAseq) and application of the deep-learning based algorithm TransCUPtomics for prediction of tissue of origin, and DNA methylation analysis were performed and compared to public renal cell carcinomas (RCC). Progression Free Survival (PFS) and Overall Survival (OS) were calculated using Kaplan-Meier estimates. Results: 23 patients were included. The median age at diagnosis was 57 yo and 17/23 were male. The most common metastatic sites were the bones (N=17) and the lymph nodes (N=14). 19/23 patients presented with at least two distinct distant metastatic sites. Genomic analyses performed in 10 patients led to the identification of recurrent inactivating mutations in genes commonly altered in RCC, including NF2 (N=7), SETD2 (N=3), or VHL (N=1). 10/11 samples analyzed by RNAseq were predicted as RCC by the TransCUPtomics classifier based on their gene expression profiles. DNA methylation profiling performed in 7 samples showed major similarity with known RCC subtypes.Centralized pathological review and integration of molecular characteristics led to the final diagnoses of papillary RCC (N=2), clear cell RCC (N=7), renal medullary carcinoma (N=1), TFEB-amplified RCC (N=1) and unclassified RCC (N=12). 20/23 patients received at least one line of systemic treatment based on the renal origin, including anti-angiogenic TKI, anti-PD1/PDL1 antibody, anti-CTLA4 antibody or mTOR inhibitor. The median PFS under the first renal-oriented systemic treatment was 5 months and 10 patients remained progression-free for more than 6 months under tailored-treatment. The median OS was 31 months, and 11 patients are still alive in October 2023. Conclusions: This study shows that rCUP represent a new entity within CUPs that shares major similarities with classical RCC despite the more frequent presentation of unfavorable prognostic factors. Prolonged survival can be observed with renal-tailored systemic treatment, supporting the individualization of these patients within CUP. Citation Format: Nicolas Jacquin, Julien Masliah-Planchon, Guillaume Grisay, Ronan Flippot, Riwan Brillet, Célia Dupain, Maud Kamal, Isabelle Guillou, Nadège Gruel, Nicolas Servant, Pierre Gestraud, Jennifer Wong, Vincent Cockenpot, Andreia Goncalves, Janick Selves, Hélène Blons, Etienne Rouleau, Oliver Delattre, Christophe Le Tourneau, Ivan Bièche, Yves Allory, Laurence Albigès, Sarah Watson. Metastatic renal cell carcinoma with occult primary: Clinical and biological evidence for a new entity of cancers of unknown primary that beneficiates from tissue-tailored treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4627.

RENO Study: Clinical characteristics, treatment patterns and survival results in patients with metastatic renal cell carcinoma in Northern Spain

BackgroundThe current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an analysis describing the clinical characteristics, treatments, and health outcomes of patients with mRCC in northern Spain. MethodsRetrospective observational study. Adult patients diagnosed with mRCC between Jan 2007 and Dec 2019 were included. Epidemiological, efficacy and toxicity data were collected. Median overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method. ResultsA total of 829 patients were included (median age at diagnosis:63 years;73% men). Median follow-up was 180 months. The preponderant histology was clear cell (85%). In 50% the initial diagnosis was advanced disease. The distribution according to IMDC prognosis was good (24%), intermediate (50%) and poor (26%). The most frequent metastatic locations were lung (68.3%) and lymph node (41.0%). Most patients (95%) received a first line (1L) systemic treatment, 60% were treated with a second line (2L) of therapy and 37% received third line (3L). A VEGFR-TKIs was the most common treatment (1L: 90%, n = 507; 2L: 49%, n = 233; 3L: 54%, n = 156) followed by mTOR inhibitors (1L: 2%, n = 4; 2L: 27%, n = 126; 3L: 23%, n = 68) and immunotherapy (1L: 3.7%, n = 25; 2L: 27%, n = 126). Median OS was 24.5 months in the general population. According to IMDC prognostic groups, OS was 52.5, 25.7 and 9 months respectively. From the start of the 1L, 2L, and 3L treatment, median PFS was: 1L: 7.8 (6.8–9.0); 2L: 4.9 (4.3–5.5); 3L: 4.3 (3.8–4.8) months. No unexpected toxicity was reported. ConclusionsThe Real-World Data on the management of mRCC in Northern Spain are comparable in epidemiology, efficacy, and safety to studies conducted in other areas of the world. The significant reduction in the number of patients receiving second and subsequent lines of therapy hampers the access to new therapies developed in this context.