A phase II study of pembrolizumab and capecitabine for triple-negative (TN) and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer (MBC)

Autor: Cesar A. Santa-Maria, Alfred Rademaker, Sarika Jain, Dean Tsarwhas, Tara Dedic, Ami N. Shah, Valerie Nelson, Lisa Flaum, Massimo Cristofanilli, Regina Uthe, William J. Gradishar, Irene Helenowski, Kelly Kindy
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Oncology. 37:1096-1096
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2019.37.15_suppl.1096
Popis: 1096 Background: Response rates to single agent immune checkpoint blockade in unselected MBC are low; however, they may be augmented when combined with chemotherapy. Methods: We conducted a single-arm, phase II study of patients with TN or endocrine-refractory MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg IV day 1 and capecitabine 1000 mg PO BID days 1-14 of a 21-day cycle. The primary endpoint was progression free survival (PFS) and secondary endpoints were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2 month (mo) improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone. Results: Thirty patients, 16 with TN and 14 endocrine-refractory MBC, were enrolled from 2017-18. Patients had a median age of 51 years and received a median of 1 prior line of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.1 mo (95% CI, 2.3-8.2 mo) and median overall survival was 15.4 mo (95% CI, 8.2-16.6 mo). ORR was 14% (n = 4), stable disease (SD) was 41% (n = 12), and clinical benefit rate (CBR = PR + SD > 6 mo) was 28% (n = 8). The ORR and CBR were similar between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and endocrine refractory, respectively). The 1-year PFS rate was 20.7% and 3 pts have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue, and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%), and diarrhea (3%), as well as grade 5 hepatic failure in a pt with liver metastases. Conclusions: Compared to historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected cohort; however, some patients had prolonged disease control. Future studies of chemo-immunotherapy in MBC with liver metastases require close safety monitoring. Clinical trial information: NCT03044730.
Databáze: OpenAIRE
Externí odkaz: