Abstract P2-09-05: LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC)
| العنوان: | Abstract P2-09-05: LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC) |
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| المؤلفون: | Trevor A. Jolly, Rachel C. Jankowitz, Hyman B. Muss, Claire Dees, Dominic T. Moore, Oludamilola Olajide, Maria J. Sambade, KE Reeder-Hayes, Rebecca Kaltman, Luz Cuaboy, CM Perou, Kristen Cowens, Carey K. Anders, Lisa A. Carey, J.S. Serody, Dante S. Bortone, Mark Woodcock, Benjamin C. Calhoun, Amy Garrett, Benjamin G. Vincent, Karen P. McKinnon, Vinay K. Gudena |
| المصدر: | Cancer Research. 79:P2-09 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Cyclophosphamide, business.industry, medicine.medical_treatment, Phases of clinical research, Pembrolizumab, Neutropenia, medicine.disease, Breast cancer, Internal medicine, medicine, Progression-free survival, business, Triple-negative breast cancer, medicine.drug |
| الوصف: | Background: While immunotherapy holds promise in the treatment of mTNBC, response rates (RR) in unselected patients (pts) are approximately 20%. Strategies to augment response to immunotherapy include depletion of regulatory T cells (Tregs). A single dose of cyclophosphamide (Cy) given prior to checkpoint inhibition achieved this goal in preclinical models of TNBC (Taylor et al., JCI, 2017). Thus, we designed a phase II study to evaluate this strategy in the clinical setting of mTNBC. Patients/Methods: In cycle 1 (C1), eligible pts with mTNBC received a single dose of Cy 300mg/m2 IV on day 1 (C1D1) followed by pembrolizumab 200mg IV on day 2 (C1D2), then every 3 weeks thereafter. The co-primary objectives were (1) progression free survival (PFS, null 1.9 mos vs. 2.9 mos, 80% power, alpha 0.05) and (2) reduction in Tregs in peripheral blood measured by flow cytometry. Secondary endpoints were response rate (RR), survival (OS), and RNA-based correlative endpoints. Results: 40 patients were evaluable for efficacy: mean age 54.5 yrs (33 – 82 yrs), 75% white, 22% black, 3% American Indian. All patients had received 1 prior line of chemotherapy in the metastatic setting; 29% received 5 or more prior lines. The most common grade 3 adverse events (AE's), all 5%, were neutropenia, anemia, elevated AST, and fatigue. Immune-related grade 3 AE's, all 3%, included colitis, dry mouth, pneumonitis. Overall RR was 21% (0 CR, 8 PR), 3 pts had stable disease. Median PFS was 1.8 months (mos) (95% CI 1.4–2.5) and OS was 6.3 mos (95% CI 2.8–8.4). There was a non-significant decrease in Tregs from C1D1 to C1D2 (-3.3%, p=0.19); but from C1D2 to C2D1, Tregs increased 21.7% (p=0.005). There was no association between changes in Tregs or number of prior lines of therapy with RR (p>0.09), while immune-related AE's were associated with response (p=0.02). Correlatives studies illustrate B cell immune gene signature expression and B cell receptor repertoire diversity were enriched in responders, while genes/pathways associated with neutrophils, anti-apoptosis, PI3K/AKT and down-regulation of MHC class 1 were associated with non-response. Conclusions: While pembroliuzumab plus Cy was well-tolerated among pts with mTNBC, efficacy was similar to historical control, likely due to minimal effect of Cy on Tregs. Correlative analyses illustrate that study of adaptive immune features, including B cell biology, is a promising strategy for understanding response to PD-1 inhibition in breast cancer. Further strategies to deplete Tregs in a more sustained manner are worthy of future exploration (NCT02768701). Citation Format: Anders CK, Moore D, Sambade M, Cuaboy L, Garrett A, Woodcock M, McKinnon K, Cowens K, Bortone D, Calhoun B, Carey L, Dees C, Jolly T, Muss H, Reeder-Hayes K, Kaltman R, Jankowitz R, Gudena V, Olajide O, Perou C, Vincent B, Serody J. LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-05. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c96275f9298996f257fa238ccddb818e https://doi.org/10.1158/1538-7445.sabcs18-p2-09-05 |
| رقم الأكسشن: | edsair.doi...........c96275f9298996f257fa238ccddb818e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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