Mukai, Hirofumi

1088 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.

Abstract Background: Patients with previously untreated mTNBC typically receive cytotoxic chemotherapy as first-line therapy for metastatic disease. However, efficacy and safety are suboptimal. KEYNOTE-086 (NCT02447003) is a multicohort, single-arm, phase 2 study of pembrolizumab monotherapy for mTNBC. In cohort B, we assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC. Methods: Key eligibility criteria for cohort B were age ≥18 y, centrally confirmed TNBC, no prior systemic anticancer therapy for metastatic disease, ECOG performance status 0-1, measurable disease per RECIST v1.1 by central review, no radiographic evidence of brain metastases, and a tumor PD-L1 combined positive score (CPS) ≥1. Pembrolizumab 200 mg was given once every 3 wk for 24 mo or until disease progression, intolerable toxicity, or investigator or patient decision. Tumor imaging was performed every 9 wk for 12 mo and every 12 wk thereafter. Clinically stable patients with radiologic progression could remain on pembrolizumab until progression was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, duration of response, and PFS (all RECIST v1.1 by central review) and OS. Results: Of the 206 patients with tumors evaluable for PD-L1 expression, 128 (62%) had PD-L1 CPS ≥1. Of these, 84 met all eligibility criteria and enrolled. All patients were women, median age was 52.5 y, 29 (35%) had ECOG PS 1, 40 (48%) had elevated LDH, 55 (65%) had visceral ± nonvisceral metastases, and 73 (87%) received prior (neo)adjuvant therapy. All patients received ≥1 pembrolizumab dose, and after median follow-up of 10.6 mo, 18 (21%) remained on pembrolizumab. Treatment-related AEs occurred in 53 (63%) patients and were of grade 3-4 severity in 7 (8%); no patients died or discontinued pembrolizumab because of treatment-related AEs. The most common treatment-related AEs were fatigue (26%), nausea (13%), and diarrhea (12%). No grade 3-4 treatment-related AE occurred in >1 patient. The most common immune-mediated AE was hypothyroidism (10%). Three patients had complete response and 16 had partial response for an ORR of 23% (95% CI 15-33). Of the 11 patients with a best response of stable disease, 1 had stable disease for ≥24 wk, leading to a disease control rate of 24% (95% CI 16-34). 12 of 19 (63%) responses were ongoing at data cutoff, and median duration of response was 8.4 mo (range 2.1+ to 13.9+). Median PFS was 2.1 mo (95% CI 2.0-2.2), with an estimated 6-mo PFS rate of 26%. Median OS was 16.1 mo (95% CI 11.3-NR), with an estimated 6-mo OS rate of 83%. Conclusions: Pembrolizumab monotherapy continues to demonstrate a favorable safety profile and robust, durable antitumor activity in patients with PD-L1-positive, previously untreated mTNBC. Citation Format: Adams S, Loi S, Toppmeyer DL, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong AC, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan A, D'Aquanno C, Ding Y, Karantza V, Schmid P. KEYNOTE-086 cohort B: Pembrolizumab monotherapy for PD-L1–positive, previously untreated, metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD6-10.