Abstract P6-10-03: KEYNOTE-012: Long-lasting responses in a phase Ib study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC)
Authors: Nanda R , Specht J , Dees C , Berger R , Gupta S , Geva R , Pusztai L , Pathiraja K , Ray A , Karantza V , Buisseret L 
Published: March 2017

Abstract
Background: In the multicenter, nonrandomized phase Ib KEYNOTE-012 trial (NCT01848834), the anti–PD-1 antibody pembrolizumab demonstrated promising antitumor activity (18.5% ORR in patients [pts] with measurable disease at baseline as assessed by RECIST v1.1 and central radiology review; 6-mo PFS rate, 24%; 12-mo OS rate, 43.1%; data cutoff date, March 23, 2015) and a manageable toxicity profile as later-line of therapy for previously treated, PD-L1+ mTNBC. Here we present updated data for the mTNBC cohort of KEYNOTE-012.
Methods: Key enrollment criteria were: age ≥18 yr; ER-negative, PR-negative, HER2-negative, recurrent or metastatic breast cancer; measurable disease based on RECIST v1.1; ECOG PS 0-1; any number of prior systemic treatments in the metastatic setting; and PD-L1+ tumors (expression in stroma or ≥1% of tumor cells by IHC using the 22C3 antibody). Pts received pembrolizumab 10 mg/kg Q2W for 24 mo or until disease progression or unacceptable toxicity. Clinically stable pts with initial evidence of radiographic progression could remain on pembrolizumab until progression was confirmed. Response was assessed every 8 wk by central radiology review based on RECIST v1.1. After pembrolizumab discontinuation, pts were followed every 3 mo until death or withdrawal of consent. OS was estimated using the Kaplan-Meier method.
Results: Thirty two female pts were enrolled. Median age was 50.5 yr (range, 29-72); 46.9% had received ≥3 lines of therapy and 25.0% had received ≥5 lines of therapy for metastatic disease. As of the data cutoff date of April 26, 2016, median follow-up duration was 10.7 mo (range, 0.4-32.7). Median OS was 10.2 mo (95% CI, 5.3-17.5) and 12-mo OS rate was 41.1%; 25 (78.1%) pts had died. Median PFS was 1.9 mo (95% CI, 1.3-4.3) and 12-mo PFS rate was 15.0%. Of the 5 responders (including 1 complete response [CR] and 4 partial responses [PR]), 3 have had long-lasting benefit from pembrolizumab. The pt with CR discontinued study medication 11 mo after achieving CR and has remained in CR for approximately 15 mo without receiving any additional anticancer treatment. Two pts with PR discontinued pembrolizumab after completing 2 yr of treatment. The first pt has maintained response for 22.7 mo; the second pt had disease progression after 7.7 mo of response and recently restarted pembrolizumab as allowed by protocol. Median duration of response has not been reached (range, 15-58+ wk). Thirty (93.8%) pts discontinued pembrolizumab (27 [84.4%] with progressive disease and 3 [9.4%] for AEs) before reaching 2 yr of treatment. Six (18.8%) pts experienced grade 3-5 treatment-related AEs; there was 1 treatment-related death (disseminated intravascular coagulation with decreased blood fibrinogen).
Conclusions: Pembrolizumab provides long-lasting responses in heavily pretreated pts with mTNBC. Further development of pembrolizumab for treatment of this poor-prognosis pt population is warranted, and a phase II study evaluating efficacy and safety of single-agent pembrolizumab as later line of treatment for mTNBC is ongoing (KEYNOTE-086, NCT02447003).
Citation Format: Nanda R, Specht J, Dees C, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Ray A, Karantza V, Buisseret L. KEYNOTE-012: Long-lasting responses in a phase Ib study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-10-03.