2017 ASCO Annual Meeting!
Session: Breast Cancer—Metastatic
Type: Poster Session
Time: Sunday June 4, 8:00 AM to 11:30 AM
Location: Hall A
Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B.
2017 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #80)
J Clin Oncol 35, 2017 (suppl; abstr 1088)
Author(s): Sylvia Adams, Sherene Loi, Deborah Toppmeyer, David W. Cescon, Michele De Laurentiis, Rita Nanda, Eric P. Winer, Hirofumi Mukai, Kenji Tamura, Anne Armstrong, Minetta C. Liu, Hiroji Iwata, Larisa Ryvo, Pauline Wimberger, Deborah Card, Yu Ding, Vassiliki Karantza, Peter Schmid; NYU Langone Medical Center, New York, NY; Peter MacCallum Cancer Centre, Melbourne, Australia; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Princess Margaret Cancer Centre, Toronto, ON, Canada; Istituto Nazionale Tumori “Fondazione G.Pascale”- IRCCS, Naples, Italy; The University of Chicago, Chicago, IL; Dana-Farber Cancer Institute, Boston, MA; National Cancer Center Hospital East, Kashiwa, Japan; National Cancer Center Hospital East, Tokyo, Japan; The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom; Mayo Clinic, Rochester, MN; Aichi Cancer Center Hospital, Nagoya, Japan; Sourasky Medical Center, Tel Aviv, Israel; Universitätsklinikum Carl Gustav Carus TU Dresden, Dresden, Germany; Merck & Co., Inc., Kenilworth, NJ; Barts Health NHS Trust, London, United Kingdom
Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003