Cycles Of Paclitaxel Research Articles

694P Sequential high-dose-chemotherapy with 4 cycles paclitaxel, ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory male germ cell cancer: Final results with 15.8 years follow-up

694P Sequential high-dose-chemotherapy with 4 cycles paclitaxel, ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory male germ cell cancer: Final results with 15.8 years follow-up

Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Evaluating the efficacy of a premedication regimen including high-dose cetirizine in reduction of hypersensitivity reactions to paclitaxel: A retrospective cohort study.

Hypersensitivity reactions (HSR) are a known adverse effect of paclitaxel, occurring in approximately 10% of patients, typically during the first or second infusion of the medication. Corticosteroids, histamine-1 and histamine-2 receptor antagonists are given prior to paclitaxel infusions to reduce the incidence of HSR. There are limited data that suggest administration of cetirizine given prior to a platinum infusion as secondary prophylaxis may reduce HSR rates. The objective of this study was to assess the impact of a novel paclitaxel hypersensitivity prevention protocol including high-dose cetirizine administered 12 and 6 h prior to paclitaxel infusion on the rate of HSR compared to a historical control. The primary objective was the rate of HSR of any grade after the first cycle of paclitaxel. Secondary outcomes included grade of infusion reaction and incidence of severe HSR. A total of 104 patients were included for analysis in the cetirizine group and 124 in the control group. Hypersensitivity reactions occurred in 37 (16.2%) patients in the overall population, and no statistical difference was observed between groups. (13.46% vs 18.55%; p = 0.23). Numerically more grade 3-4 HSRs occurred in the control group than the treatment group (30.77% vs 69.23; p = 0.51). The addition of cetirizine to paclitaxel infusions resulted in numerically lower rates of HSR and a reduction in severity of grade 3-4 HSRs. Future studies with more robust compliance data and a larger patient population would be needed to appropriately assess the efficacy of our novel treatment regimen.

Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study.

In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab plus chemotherapy and then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522. Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel plus carboplatin and then 4 cycles of doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1 of cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with at least 60% completion and at least 80% compliance were assessed using a longitudinal model (no alpha error assigned). Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab plus chemotherapy [n = 762] vs placebo plus chemotherapy [n = 383]) in LS mean change from baseline to week 21 in QLQ-C30 global health status/quality of life (GHS/QoL), emotional functioning, and physical functioning were -1.04 (95% confidence interval = -3.46 to 1.38), -0.69 (95% CI = -3.13 to 1.75), and -2.85 (95% CI = -5.11 to -0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [n = 539] vs placebo [n = 308]) in LS mean change from baseline to week 24 were -0.41 (95% CI = -2.60 to 1.77), -0.60 (95% CI = -2.99 to 1.79), and -1.57 (95% CI = -3.36 to 0.21). No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo plus chemotherapy in early-stage TNBC. ClinicalTrials.gov, NCT03036488.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial

The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. Patients were randomized 1:1 to receive camrelizumab (200mg) or placebo, both in combination with up to six cycles of paclitaxel (175mg/m2) and cisplatin (75mg/m2). All treatments were administered intravenously every 3weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p<0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Effectiveness of increasing the scalp cooling duration to prevent alopecia during adjuvant chemotherapy for breast cancer: a randomized pilot study

PurposeAlopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation.MethodsPatients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss.ResultsThe success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039).ConclusionLong duration scalp cooling during chemotherapy might increase patients’ discomfort and does not appear to improve hair preservation.

Conversion surgery for tislelizumab combined chemotherapy for T4a/N3 esophageal squamous cell carcinoma (ESCC): A prospective, single-arm, phase II study.

4069 Background: T4a/N3 ESCC is treated with neoadjuvant concurrent chemoradiotherapy plus surgery or radical chemoradiotherapy according to NCCN guidelines. This study aimed to evaluate the safety and efficacy of conversion therapy of Tislelizumab combined with chemotherapy in patients with T4a/N3 ESCC. Methods: This is a prospective, single-arm, single-center clinical trial. A total of 40 patients with newly diagnosed ESCC (cT4a/N3) received 2-4 cycles of paclitaxel (135 mg/m2) on day 1, and cisplatin (80 mg/m2) on day 1, Tislelizumab (200 mg) on day 2, every 3 weeks. After an efficacy evaluation, the patients will undergo radical esophagectomy resection within 4-6 weeks after conversion therapy. The primary endpoints are the safety and the R0 resection rate. The secondary endpoints include the objective response rate (ORR), a postoperative pathological complete response (pCR), major pathological response (MPR), overall survival (OS), disease-free survival (DFS). Exploratory endpoint is to examine immune biomarker of the efficacy of conversion therapy for ESCC. Results: 40 patients were enrolled, the ORR was 95%(38/40), and 60% (24/40) patients who completed conversion treatment underwent esophagectomy. R0 resection rate was 100% (24/24) with no reoperations or perioperative deaths. 70% (28/40) patients experienced at least one treatment-related adverse event (TRAE) and 12.5% (5/40) patients reported grade 3 and above TRAEs. For these surgical patients, the MPR and pCR rates were 33% (8/24) and 20.8% (5/24) respectively. Flow cytometry showed that the percentage of CD3+CD4+CD8-T cells was significantly increased in peripheral blood after conversion therapy (p-value 0.02). Conclusions: Tislelizumab combined with chemotherapy, followed by radical esophagectomy resection has promising efficacy and good safety for T4a/N3 ESCC. Clinical trial information: NCT05449483 .

Final analysis of the randomized phase 3 ESCORT-1st trial: Camrelizumab plus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma.

4055 Background: The ESCORT-1st trial (NCT03691090) was a randomized, double-blind, placebo-controlled, phase 3 trial that aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy compared to placebo plus chemotherapy in previously untreated patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Interim analysis of this trial showed significantly longer overall survival (OS) and progression-free survival (PFS) with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (Luo et al., JAMA, 2021). In this report, we present the final analysis of the efficacy and safety outcomes from the ESCORT-1st study, with an additional 1.5-year follow-up. Methods: A total of 596 eligible patients with previously untreated advanced or metastatic ESCC were randomly assigned in a 1:1 ratio to receive either camrelizumab 200 mg or placebo for up to 2 years, in combination with up to 6 cycles of paclitaxel and cisplatin. All treatments were administered intravenously every 3 weeks. Randomization was stratified based on the presence of liver metastases and previous definitive chemoradiotherapy. The primary endpoints of the study were OS and PFS as assessed by an independent review committee. The data cutoff for this final analysis was April 30, 2022. Results: At the data cutoff, the minimum follow-up period was 24 months, and no patients remained on the study treatment. Among the patients, 214 (71.8%) in the camrelizumab plus chemotherapy group and 250 (83.9%) in the placebo plus chemotherapy group had died. The camrelizumab plus chemotherapy group demonstrated a longer median OS compared to the placebo plus chemotherapy group (15.6 months [95% CI 14.0–18.4] vs 12.6 months [95% CI 11.2–13.8], HR 0.70 [95% CI 0.58–0.84]; one-sided P&lt;0.0001). The 1-year, 2-year, and 3-year OS rates were 62.4% vs 51.7%, 35.9% vs 23.8%, and 25.6% vs 12.8% in the camrelizumab plus chemotherapy group and the placebo plus chemotherapy group, respectively. The median investigator-assessed PFS was also longer with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (7.6 months [95% CI 6.9–8.3] vs 5.8 months [95% CI 5.6–6.6]; HR 0.54 [95% CI 0.45–0.65]; one-sided P&lt;0.0001). No new safety signals were identified during the extended follow-up period. Conclusions: The extended follow-up of the ESCORT-1st trial reaffirms that camrelizumab plus chemotherapy provides significant and clinically meaningful improvements in OS and PFS compared to placebo plus chemotherapy, with a manageable safety profile for patients with untreated advanced or metastatic ESCC. These findings further support the use of first-line camrelizumab plus chemotherapy as the standard of care for these patients. Clinical trial information: NCT03691090 .

Repurposing hemostatic drug desmopressin in AVPR2-expressing triple-negative breast cancer: Target expression analysis and preclinical antineoplastic effects on tumor growth and metastatic progression.

e15087 Background: Desmopressin (dDAVP) is a hemostatic drug that acts as an agonist of the arginine vasopressin receptor 2 (AVPR2) that is present in vascular and malignant cells. Preclinical data show that dDAVP triggers cytostatic mechanisms, blocking angiogenesis and reducing metastases by limiting the survival of circulating tumor cells. Triple-negative breast cancer (TNBC) is associated with poor prognosis due to limited response to therapy and frequent early metastatic recurrence. Considering the unsatisfied clinical need for novel therapeutic options in TNBC, we evaluated the antitumoral activity of dDAVP on experimental models of TNBC, alone or in addition to chemotherapy. We also assessed the expression and clinical impact of AVPR2 in breast cancer samples. Methods: Human and murine TNBC cell lines were used for in vitro experiments. Target expression was assessed by qPCR and immunohistochemistry (IHC), in experimental or clinical tumors (NCT01606072). Effects of dDAVP were evaluated by proliferation, clonogenic, 3D growth and chemotaxis assays, qPCR arrays, and confocal microscopy. Local and distant tumor progression were assessed in vivo in nude or BALB/c mice. TIMER2.0 and UCSC Xena platforms (BRCA TCGA /n = 1260) were used for bioinformatic studies. Results: dDAVP significantly reduced growth and chemotaxis of AVPR2-expressing TNBC cells. Cytostatic effects of dDAVP were associated with altered actin cytoskeleton dynamics and differential expression of angiogenesis and metastasis-related genes. Cooperative effects were observed in vitro and in vivo after combining dDAVP with taxane or alkylating therapy. Tumor-bearing mice were treated with intravenous injections of dDAVP (0.3 µg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.) or carmustine (25 mg/kg i.p.). Combination regimens resulted in greater survival and tumor growth and metastasis inhibition. Bioinformatic analysis of the TCGA database showed that AVPR2 had a positive prognostic impact on overall survival in breast cancer patients, especially in the basal-like molecular subtype. AVPR2 also correlated with different immune cell infiltrates such as NK and dendritic cells, and CD4+ and CD8+ T cells. Moreover, AVPR2 expression was detected by IHC in 6/18 breast cancer clinical samples using a small cohort of surgical specimens. Conclusions: AVPR2 expression is associated with improved outcomes in patients with TNBC. Agonist activation of AVPR2 using dDAVP leads to cancer cell growth inhibition in TNBC cell lines and mouse models. We propose dDAVP as a potential novel therapeutic option for treating TNBC either as monotherapy or in combination with chemotherapy. The therapeutic impact of its addition to immune checkpoint inhibitors remains to be explored.

A propensity-matched cohort study of neoadjuvant immunotherapy combined with chemotherapy versus neoadjuvant chemotherapy for early-stage triple-negative breast cancer.

e13134 Background: Preferred neoadjuvant treatment (NAT) regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. This study compared the efficacy, safety and biomarker exploration of camrelizumab combined with chemotherapy and chemotherapy as neoadjuvant treatment for early-stage TNBC. Methods: This study included 2 cohorts with different NAT regimens, matched (2:1) according to age, clinical T and N stage, and Ki-67 status. Patients in the immune combination chemotherapy (NIC) cohort were recruited from a phase II clinical trial (NCT04676997). NIC patients received intravenous camrelizumab at a dose of 200mg and simultaneous chemotherapy consisted of platinum-free drugs, or platinum containing drugs. Patients in the neoadjuvant chemotherapy (NAC) cohort regimen comprised 4 cycles of paclitaxel 175 mg/m2, and 4 cycles of epirubicin (90 mg/m2, d1, q2w) + cyclophosphamide (600 mg/m2, d1, q2w). The indicators of this study include pCR, breast pCR (bpCR), axillary lymph node dissection (ALND) rate, breast conserving surgery (BCS) rate and tumor immune microenvironment (TIME) analysis of gene expression profiling. Results: Of 252 eligible patients, 162 patients were identified in the analysis after propensity score matching (PSM). Compared with NAC alone, the addition of camrelizumab brought higher pCR rates (64.81% versus 37.04%, p&lt;0.05), ALND rates (38.89% versus 12.96%, p&lt;0.05) and comparable BCS rates (20.37% versus 15.74%, p&lt;0.05). Gene expression analysis was performed on tumor tissue samples from 12 patients receiving NAC and 16 patients receiving NIC before and after NAT. The results showed that the TIME status of the NIC and NAC groups before treatment was basically the same. Moreover, we respectively compared the TIME status of patients with pCR and non_pCR in NIC and NAC before NAT. The results found that there were 9 significantly different signatures (p&lt;0.05) between pCR and non_pCR patients in the NIC group, and 1 signature (p&lt;0.05) in the NAC group, respectively. Notably, we found 8 signatures (B Cells, CD8 T Cells, TIS, IFN Gamma, Lymphoid, T Cell, APM, Immunoproteasome), that were scored significantly higher only in pCR patients in the NIC group compared with non-pCR patients, and 8 signatures could promote response to immunotherapy. The common difference signature between the two groups is Treg cells. Conclusions: In patients with early-stage TNBC, neoadjuvant treatment with camrelizumab plus chemotherapy significantly improved pCR with an acceptable safety profile. Differences in TIME may affect response to treatment regimens. Future validation in prospective randomized controlled trials with larger sample sizes is needed. Clinical trial information: NCT04676997 .

Late coronary artery injury following chemoradiotherapy for thymic carcinoma: a case report

IntroductionSurgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients’ long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy.Case presentationThe male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components.ConclusionsChemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.

Efficacy and safety of chemotherapy as monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer: a single-center retrospective analysis

ObjectiveThe aim of this study is to explore the efficacy and safety of chemotherapy (CT) as a monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer.MethodsA retrospective analysis was conducted on the medical records of patients diagnosed with stage IB-IIA cervical cancer who underwent radical hysterectomy at the People’s Hospital of Suzhou High-tech District between 2010 and 2020. A total of 66 patients with intermediate or high-risk factors for recurrence were treated exclusively with CT. This cohort included 42 patients in the intermediate-risk group and 24 in the high-risk group. Treatment protocols consisted of 4–6 cycles of paclitaxel and cisplatin drugs for the intermediate-risk group, and 6 cycles for the high-risk group. The relapse-free survival (RFS), recurrence rates, and common CT-related adverse reactions, including bone marrow suppression, nausea and vomiting, and diarrhea, were assessed for both groups.Results(1) The cumulative 3-year RFS rates for the intermediate-risk and high-risk groups were 97.3% (36/37) and 82.4% (14/17), respectively, with cumulative 5-year RFS rates of 97.1% (34/35) and 82.4% (14/17), respectively. The Log rank test revealed no significant difference between the two groups (P > 0.05), (χ² = 2.718, P = 0.099). The 5-year recurrence rates in the intermediate-risk and high-risk groups were 2.38% (1/42) and 12.50% (3/24), respectively. (2) The incidence of grade III bone marrow suppression in the intermediate-risk and high-risk groups was 21.19% (11/42) and 25.00% (6/24), respectively, while the incidence of grade IV bone marrow suppression was 11.90% (5/42) and 8.33% (2/24), respectively. There was no statistically significant difference in bone marrow suppression grades between the two groups (P > 0.05).ConclusionCT with paclitaxel and cisplatin, administered as monotherapy post-radical hysterectomy for stage IB-IIA cervical cancer, demonstrates satisfactory survival benefits with an acceptable safety profile. Moreover, no significant differences were observed in prognosis or adverse reactions between the different risk groups treated solely with CT.

Breast Carcinoma with Isolated Orbital Metastasis –A Rare Clinical Entity

Breast cancer with isolated orbital metastasis is a rare clinical entity.We hereby present a rare case report of 35 year old premenopausal lady with known case of carcinoma breast right side (operated for right modified radical mastectomy in year 2017 with final histopathology of pT2N2M0, hormone receptor-positive and Her2-negative disease). She completed adjuvant 8 cycles of standard dose chemotherapy with 4 cycles of Cyclophosphamide, Adriamycin followed by 4 cycles of Paclitaxel followed by local Radiation therapy. She was initiated Tab. Tamoxifen 20 mg once daily and was continued same for 4 years when in July 2021, she complained of sudden decreased visual acuity and diplopia of right eye lasting from last 1 month. Ophthalmological examination confirmed the findings with decreased visual acuity of 6/36 of right eye while visual acuity of left eye was normal. CT scan of orbits revealed 28 × 18mm heterogeneous enhancing soft tissue mass in right orbital compartment,extrabulbar, occupying postero-superior quadrant inseparable from lateral rectus muscle with optic nerve effacement. PET-CT scan was performed which revealed no metastasis elsewhere in the body. She was offered surgical oophorectomy followed by switch to another hormonal therapy of aromatase inhibitors. She showed complete response to treatment and is now disease from last 2 years.

Abstract PO3-20-09: METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA

Abstract Metaplastic breast carcinoma is a rare histologic subtype of breast carcinoma, accounting for only 0.2 to 2% of all breast cancers. It is comprised of a heterogeneous histology involving mesenchymal and epithelial components. Metaplastic breast carcinoma usually harbors a triple-negative phenotype, but carries a worse prognosis compared to other breast cancer subtypes. Due to its unique histopathological and molecular characteristics, there has been limited data on the optimal management of metaplastic breast carcinoma. Moreover, the presence of a secondary breast neoplasm in the background of a prior ovarian carcinoma represents a diagnostic and therapeutic challenge. We report a case of a 55-year-old female with a previous history of serous ovarian carcinoma six years ago, who presented with an enlarging right breast mass. Digital mammography showed a right retro-areolar mass, 5.7 x 4.8 x 5.4 cm, BIRADS 4C. Initial biopsy done showed presence of atypical cells in a background of cystic change. The patient underwent modified radical mastectomy with incision biopsy and frozen section. Final histopathologic diagnosis was consistent with metaplastic breast carcinoma, mixed epithelial and mesenchymal type, Nottingham grade 2, with no lymphovascular invasion identified, pT2N0. Tumor was ER negative, PR negative, Her 2 neu negative, with Ki-67 of 10% on immunohistochemistry. She then underwent adjuvant treatment with 6 cycles of paclitaxel and carboplatin. Six years prior, the patient was likewise diagnosed with high-grade serous ovarian carcinoma. She had total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy with 6 cycles of Paclitaxel and Carboplatin was given. She had recurrence in the paraaortic lymph node after 3 years and underwent cytoreductive surgery with excision of nodule and hyperthermic intraperitoneal chemotherapy with cisplatin. Currently, the patient has no evidence of disease in the recent positron emission tomography scan, with normal serum CA-125 level. The current standard of care for metaplastic breast carcinoma follows that of triple-negative breast cancer. However, previous literature has shown that metaplastic breast carcinoma is more chemo-refractory compared to triple-negative breast cancer, with more response seen with taxane-based chemotherapy. Due to poor response rates to neoadjuvant chemotherapy, surgical management for early-stage disease is warranted. Targeting molecular alterations is necessary to improve the prognosis of this subtype. Genomic features of homologous recombination deficiency were also found to be more prevalent in metaplastic breast cancer, thus genomic testing is warranted, especially in the setting of a prior history of ovarian carcinoma. Citation Format: Raye Angeli Abella, Carlos Dy. METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA [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 PO3-20-09.

Abstract LBO1-01: Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 study

Abstract Background: In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro showed statistically significant and clinically meaningful improvements in pathological complete response (pCR) and event-free survival (EFS) compared with neoadjuvant placebo (pbo) plus chemo followed by adjuvant pbo in patients (pts) with early-stage triple-negative breast cancer (TNBC). Here, we present updated EFS results after a median follow-up of ~5 y. Methods: Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per American Joint Committee on Cancer) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause). Results: 1174 pts were randomized to pembro (n=784) or pbo (n=390) group. At data cutoff (March 23, 2023), median follow-up was 63.1 mo. 145 pts (18.5%) in the pembro group and 108 pts (27.7%) in the pbo group had an EFS event (hazard ratio [HR] 0.63 [95% CI, 0.49-0.81]). The 60-mo EFS rate (95% CI) was 81.3% (78.4-83.9) vs 72.3% (67.5-76.5), respectively; the median was not reached in either group. The benefit of neoadjuvant pembro + chemo followed by adjuvant pembro versus neoadjuvant chemo alone was consistent with the primary EFS results in all 5 sensitivity analyses, showing durable and robust EFS benefit in the pembro arm. The EFS benefit with pembro was consistent across prespecified subgroups, including PD-L1 expression, nodal status, disease stage, menopausal status, HER2 status, and lactate dehydrogenase (LDH) level (table). In a prespecified, non-randomized, exploratory analysis, 5-yr EFS rates in the pembro and pbo groups were 92.2% vs 88.2% in pts with a pCR, and 62.6% vs 52.3% in pts without a pCR. Additional analyses will be included in the presentation. Follow-up for OS is ongoing Conclusions: Neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful improvement in EFS compared with neoadjuvant chemo alone in pts with early-stage TNBC. This is seen across subgroups and regardless of the pCR outcome. Table. EFS results in overall population and by subgroup Citation Format: Peter Schmid, Javier Cortés, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Küemmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Theodoros Foukakis, Marie-Ange Mouret-Reynier, Marta Ferreira, Seock-Ah Im, Fatima Cardoso, Yu Ding, Wilbur Pan, Konstantinos Tryfonidis, Joyce O'Shaughnessy. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 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 LBO1-01.

Abstract PO2-01-05: Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world study

Abstract Background Pyrotinib is a new oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that targets human epidermal growth factor receptor 1 (HER1), HER2, and HER4. Previous studies have confirmed it combined with capecitabine is safe and well-tolerated in advanced breast cancer. And also PHEDRA trial had demonstrated the efficacy and safety of pyrotinib combined with trastuzumab and docetaxel neoadjuvant therapy early HER2-positive breast cancer. However, the efficacy of pyrotinib plus trastuzumab-based in real-world neoadjuvant therapy for early breast cancer is unknown. Purpose The present study aimed to explore the efficacy of pyrotinib-based in neoadjuvant therapy for early breast cancer in real-world. Method This is investigator-initiated phase 2 real-world study recruited eligible patients, aged 18–70 years with invasive carcinoma, cT2-3N0-3M0 stage, HER2-positive breast cancer. The patients received 400 mg pyrotinib orally once per day for 21 days and trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) plus different standard chemotherapy, including six 21-day cycles of docetaxel (75 mg/m2) plus carboplatin (6 mg/mL/min), or four cycles of epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) and four cycles paclitaxel (80 mg/m2). The primary endpoint was to calculate the number of patients who achieved a pathological complete response (pCR, ypT0/is, ypN0). (ChiCTR2100052892). Result The results of the 23 patients were reported, The pCR of 12 (52.2%) patients, who reached the threshold for the design, was noted. The study is ongoing. The most frequent grade 3 to 4 adverse events were diarrhea (35.6%), which all the patients received primary prevention of diarrhea, leukopenia (44.8%), and anaemia (23.7%). However, no treatment-related deaths were recorded. Conclusion Previous studies have shown the efficacy and safety of pyrotinib plus trastuzumab and docetaxel in neoadjuvant therapy of HER2-positive early breast cancer. The current trial suggests that pyrotinib plus trastuzumab-based standard chemotherapy in real-world has promising efficacy and manageable toxicity in patients with HER2-positive early breast cancer in a neoadjuvant setting, the trial is ongoing, we will enroll more patients. Citation Format: Jun Zhou, Rui Wang. Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world 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 PO2-01-05.

Abstract PO4-20-09: Successful outcome of locally advanced HR+HER2+ breast cancer treatment in a young female after pancreas-kidney transplantation. 3-year follow-up

Abstract Background Solid organs recipients with subsequent cancer comprise a group of patients with unmet medical needs: they lack any clinical trials or guidelines for treatment. There are only individual case reports in literature. Meanwhile their number is growing due to achievements in transplantology and improved cancer diagnosis. Case presentation А young 34-year-old female attended our center in September 2019 with a palpable mass and peau d'orange of the left breast. A core-needle biopsy of the left breast mass revealed invasive ductal carcinoma G3, estrogen receptor 7 (Allred), progesterone receptor 6 (Allred), HER-2 (3+), Ki-67 49%. Left axillary lymph node biopsy revealed metastatic breast cancer. After a complete examination the clinical stage was cT4bN1fM0, IIIB stage. The patient had a history of Type 1 diabetes mellitus since 2003 leading to multiple complications including terminal diabetic nephropathy, which required renal replacement therapy with the use of long-term hemodialysis since July 2014. The other complications consisted of severe retinopathy with corneal transplantation on the left eye in April 2013, an episode of right eye hemophthalmia in March 2016 with consequent loss of vision in the right eye, polyneuropathy, gastropathy and enteropathy. The patient underwent a simultaneous pancreas-kidney transplantation in April, 2016 and was on permanent immunosuppressive therapy with tacrolimus 8 mg daily and methylprednisolone 8 mg daily. The function of both transplants was satisfactory. This unique case was published by Pinchuk A. et al. in Transplant Proceedings, 2017 [doi: 10.1016/j.transproceed.2017.10.005]. A multidisciplinary approach was applied to tailoring treatment plan for this patient. Initially immunosuppressive therapy was modified: the patient discontinued methylprednisolone and started everolimus with simultaneous tacrolimus dose reduction (their doses adjusted according to blood concentrations). The tumor board decision was to start neoadjuvant therapy with regimen with the mildest and the most manageable toxicity profile and to avoid anthracyclines. From October to December 2019 the patient received 12 cycles of paclitaxel 80 mg/m2 day 1 weekly and 4 cycles of anti-HER2 dual blockade: trastuzumab 8 mg/kg day 1 followed by 6 mg/kg day 1 every 21 days + pertuzumab 840 mg day 1 followed by 420 mg day 1 every 21 days. Adverse events were: stomatitis grade 1, palmar-plantar erythrodysesthesia grade 1, diarrhea grade 2. Partial response was evaluated in the end of December 2019, but due to persistent skin edema, she was not a candidate for surgical treatment. The tumor board decision was to proceed with T-DM1 + pertuzumab based on the results of the KRISTINE trial [doi:10.1016/s1470-2045(17)30716-7]. From January to March 2020 the patient received 4 cycles of trastuzumab-emtansine 3,6 mg/kg day 1 every 21 days + pertuzumab 420 mg day 1 every 21 days. The patient tolerated this treatment with mild toxicity: ALT &amp; AST increase grade 2 and diarrhea grade 2. Considering that the edema was significantly reduced, surgical treatment was planned. The patient underwent a modified radical mastectomy for left breast cancer on 14 of April 2020. The pathological stage was ypT1аN0 R0, RCB I. The patient continued trastuzumab emtansine until November 2020 (up to 1 year of anti-HER2 targeted therapy) in the adjuvant setting. In June 2020 she underwent locoregional radiation therapy. Tamoxifen with ovarian function suppression (LHRH agonists) for 5 years was started in June 2020. Fortunately, after 3 years of follow-up after surgery there is no evidence of disease and no delayed cancer treatment complications. Conclusion: Personalized multidisciplinary team decisions for cancer patients after organ transplantation are crucial to further improve the long-term outcome of these patients. Citation Format: Lyudmila Zhukova, Natalya Polshina. Successful outcome of locally advanced HR+HER2+ breast cancer treatment in a young female after pancreas-kidney transplantation. 3-year follow-up [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 PO4-20-09.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Neoadjuvant Chemotherapy in Patients with HER2-Negative Breast Cancer: A Report from Clinical Breast Cancer Registry of Iran.

Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens. A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC). Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates. This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates.

A Rare Combination of Breast, and Thyroid Carcinoma, with Superadded COVID-19 Infection in Mother: Struggle of a Doctor as a Daughter – Case Report

Introduction: COVID-19 pandemic has severely affected the diagnosis and management of cancer patients to a large extent, with many patients being diagnosed at a later stage, and many are not able to get appropriate treatment. Furthermore, cancer patients are more prone to suffer from severe COVID-19 infection and its associated morbidity and mortality. Breast cancer is one of the commonest cancers affecting women worldwide and its number is projected to increase sharply in the post- COVID-19 era due to a serious fall in screening modalities, as patients stopped reporting to the hospital because of lockdown, movement restrictions, and fear of contracting the infection. Case Presentation: The present case report briefs a mother's sufferings and the impact it has on a daughter who is a doctor herself. It reports a rare combination of two primaries in the breast and thyroid in an asymptomatic patient with a rare mutation of the BLM gene detected incidentally. The patient was successfully operated on for stage IB ductal carcinoma breast with hemithyroidectomy and was put on chemotherapy with Cyclophosphamide 1000mg (600mg/m2) and Doxorubicin 100 mg (60mg/m2) per cycle on day one every fortnightly followed by four cycles of Paclitaxel 175mg/m2 every fortnightly. After the second cycle, the patient developed severe neutropenia and COVID-19 infection with atypical symptoms that severely involved her lungs, leading to the loss of the patient. Conclusion: With the onset of the COVID-19 pandemic, thousands of cancer patients have lost their lives, not due to cancer directly but due to failed early detection, treatment, loss of follow-up, and superadded severe COVID-19 infection.