Standard of care for mTNBC is chemo but associated with short duration of response and considerable toxicity. KEYNOTE-119 (NCT02555657) is a randomized, open-label, phase III study of pembro vs chemo as 2nd- or 3rd-line treatment for patients (pts) with mTNBC. Results for the Asia-Pacific (AP) subpopulation are presented.
Pts were ≥18 y with stage IV/M1 TNBC that progressed on or after 1-2 prior treatments, including anthracycline and/or taxane. Pts were stratified by PD-L1 status (positive [combined positive score {CPS} ≥1] vs negative [CPS <1]) and history of (neo)adjuvant treatment vs de novo metastatic disease. Pts were randomly assigned 1:1 to pembro 200 mg IV Q3W or physicians’ choice of single-agent chemo (capecitabine, eribulin, gemcitabine, or vinorelbine). Response assessed by CT/MRI Q9W for first year and Q12W thereafter. Primary end points: OS in pts with PD-L1+ tumors (CPS ≥10, ≥1) and in all pts. Secondary end points: PFS, ORR, and DOR per RECIST v1.1. Exploratory end points: OS, PFS, ORR, and DOR in pts with PD-L1+ tumors (CPS ≥20).
Of 622 pts, 181 were included in the AP group (n=83 pembro; n=98 chemo). Median time from randomization to data cutoff: 31.4 and 32.8 mo in pembro and chemo arms, respectively. Approximately half of pts had PD-L1+ tumors (CPS ≥1, n=103 [57%]; CPS ≥10, n=46 [25%]; CPS ≥20, n=24 [13%]). Median OS with pembro vs chemo was 15.6 vs 17.8 mo in pts with CPS ≥10, 12.2 vs 15.1 mo in pts with CPS ≥1, 11.6 mo vs 13.8 mo in all pts, and 23.5 vs 19.1 mo in pts with CPS ≥20. Median PFS in all pts was 2.1 mo with pembro vs 4.1 mo with chemo. ORR was 12% (n=10) in pembro and 13% (n=13) in chemo; 3 pts in each arm had complete response. Median DOR was 13.4 mo in pembro and 8.4 mo in chemo. Grade 3/4 TRAEs were in 16% and 45% of pts in pembro and chemo arms, respectively. No deaths from TRAEs occurred.
Pembro did not show improved OS vs chemo in the AP subpopulation, but in an ad hoc analysis of pts with CPS ≥20, there was a numeric improvement in OS vs chemotherapy. Additionally, DOR for all pts was numerically higher with pembro vs chemo. Pembro was well tolerated, vs chemo. Results in the AP subpopulation were consistent with the global population.
NCT02555657; September 21, 2015.
Medical writing and/or editorial assistance was provided by Matt Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
S-A. Im: Research grant/Funding (self): AstraZeneca, Novartis, Pfizer, Roche; Travel/Accommodation/Expenses: Amgen, Eisai, Hanmi, Lilly, Novartis, Pfizer, Roche; Advisory/Consultancy: MSD; Leadership role: Dae Woong. J. Cortes: Advisory/Consultancy: Rocher, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Serview, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, boehringer Ingelheim, Kyowa Kirin; Honoraria (self): Roche, Celgene, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Novartis, Eisai, Pfizer, Samsung Bioepis; Research grant/Funding (institution): Roche, AstraZeneca, Merck Sharp & Dohme, Eisai, Pfizer, Ariad Pharmaceuticals, Baxalta GMBH/Serview Affaires, Bayer Healthcare, Guardanth Health, Piqur Therapeutics, Puma C, Queen Mary University of London; Travel/Accommodation/Expenses: Roche, Daiichi Sankyo, Novartis, Eisai, Pfizer; Shareholder/Stockholder/Stock options: MedSIR. A. Goncalves: Non-remunerated activity/ies: Roche, AstraZeneca, Novartis, Pfizer. K-S. Lee: Travel/Accommodation/Expenses: Roche, Lilly, Novartis; Non-remunerated activity/ies: Dong-A Pharm. P. Schmid: Honoraria (self): AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche; Research grant/Funding (institution): AstraZeneca, Novartis, Roche, Astellas, Genentech, Oncogenex. L. Testa: Advisory/Consultancy: MSD, Lily, Novartis, Genomic Health; Non-remunerated activity/ies: Lilly, Novartis, Pfizer, Roche, Libbs; Travel/Accommodation/Expenses: Pfizer, Roche, Libbs, United Medical. I. Witzel: Travel/Accommodation/Expenses: Amgen, Pfizer, Novartis, Roche, MSD. S. Ohtani: Honoraria (institution): Chugai, AstraZeneca, Pfizer, Lilly, Eisai. N. Harbeck: Honoraria (self): BMS, MSD, Roche. F. Andre: Research grant/Funding (self): Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly. R. Dent: Honoraria (self): AstraZeneca, Merck, Pfizer, Roche, Eisai, Novartis, Lilly; Travel/Accommodation/Expenses: Roche. J. Lin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. V. Karantza: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. J.A. Mejia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. E.P. Winer: Honoraria (self): Roche, Genentech. All other authors have declared no conflicts of interest.