In KEYNOTE-355 (NCT02819518), pembro + chemo significantly improved PFS vs chemo in previously untreated locally recurrent inoperable or metastatic TNBC with tumor PD-L1 combined positive score (CPS) ≥10. We evaluated outcomes among pts in KEYNOTE-355 enrolled at sites in Asia.
Pts with de novo or locally recurrent inoperable/metastatic TNBC with disease-free interval ≥6 mo were randomized 2:1 to pembro vs pbo (up to 35 administrations) + chemo (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) until completion or progression/toxicity. Pts were stratified by chemo (taxane vs gemcitabine/carboplatin), PD-L1 CPS (≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Primary endpoints were PFS (RECIST v1.1 by BICR) and OS in the intent-to-treat (ITT) population (pop) and in PD-L1–positive pts (CPS ≥10 and ≥1). Median PFS was estimated using the Kaplan-Meier method. HRs and 95% CIs were from a Cox regression model. AEs were monitored until 30 d post-treatment (90 d for serious AEs; NCI CTCAE v4.0). No alpha was assigned to this Asian subgroup analysis.
As of Dec 11, 2019, 160 pts were enrolled from Hong Kong, Japan, Korea, Malaysia, and Taiwan (pembro + chemo, n = 113; chemo, n = 47). Median follow-up was 25.7 mo. Pembro + chemo improved PFS vs chemo in the ITT pop; the treatment effect increased with PD-L1 enrichment (Table). Incidence of grade ≥3 treatment-related AEs was 78% with pembro + chemo vs 79% with chemo (no deaths in either group).
Consistent with the overall pop, pembro + chemo showed clinically meaningful improvement in PFS vs chemo in the ITT pop and in PD-L1–positive pts enrolled in Asia with previously untreated locally recurrent inoperable or metastatic TNBC. The benefit was most pronounced in pts with PD-L1 CPS ≥10. Pembro + chemo was tolerable in these pts. C, chemo; P, pembro. *Overall population: P + C (n = 220), C (n = 103). †Overall population: P + C (n = 425), C (n = 211). ‡Overall population: P + C (n = 566), C (n = 281).
Population Treatment Median PFS, mo HR (95% CI) CPS ≥10* P + C (n = 38) 17.3 0.45 (0.22–0.91) C (n = 18) 5.6 CPS ≥1† P + C (n = 81) 7.7 0.56 (0.36–0.89) C (n = 36) 5.6 ITT‡ P + C (n = 113) 8.8 0.61 (0.41–0.90) C (n = 47) 6.7
NCT02819518.
Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, 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.
D.W. Cescon: Honoraria (self): Novartis; Pfizer; Advisory/Consultancy: Agendia; AstraZeneca; Genomic Health; GlaxoSmithKline; Merck; Novartis; Pfizer; Puma Biotechnology; Roche/Genentech; Research grant/Funding (institution): GlaxoSmithKline; Merck; Pfizer; Roche/Genentech; Licensing/Royalties, Patent pending (assigned to institution): Biomarkers of TTK inhibitors. H.S. Rugo: Research grant/Funding (institution), Financial support for clinical trials: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, Sermonix, and Immunomedics; Advisory/Consultancy: Puma; Samsung. S-A. Im: Advisory/Consultancy: Amgen; AstraZeneca; Eisai; Hanmi; Lilly; Medpacto, Inc.; Novartis; Pfizer; Roche/Genentech; Research grant/Funding (self): AstraZeneca; Pfizer; Roche/Genentech; Travel/Accommodation/Expenses: Novartis; Roche/Genentech. C. Gallardo: Advisory/Consultancy: Lilly; MSD; Roche; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Research grant/Funding (self): Novartis Pharma SAS; Roche; Travel/Accommodation/Expenses: MSD; Roche. C.H. Barrios: Advisory/Consultancy: Boehringer Ingelheim; Eisai Europe Ltd.; GlaxoSmithKline; Novartis Pharma SAS; Pfizer Pharmaceuticals Israel; Roche/Genentech; Research grant/Funding (self): AB Science; Abraxis BioScience; Amgen; Asana Biosciences; Astellas Pharma; AstraZeneca; Biomarin; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Exelixis; GlaxoSmithKline; ImClone Systems; LEO Pharma; Lilly; Medivation; Merck; Merrimack; Mill; Research grant/Funding (self), Investigator in AbbVie-sponsored clinical trials: AbbVie. H. Iwata: Honoraria (self): AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Kyowa Hakko Kirin; Lilly Japan; Novartis; Pfizer; Advisory/Consultancy: AstraZeneca; Chugai Pharma; Daiichi Sankyo; Kyowa Hakko Kirin; Lilly Japan; Novartis; Pfizer; Research grant/Funding (institution): AstraZeneca; Bayer; Chugai Pharma; Daiichi Sankyo; Eisai; GlaxoSmithKline; Kyowa Hakko Kirin; Lilly Japan; MSD; Nihonkayaku; Novartis; Pfizer. N. Masuda: Leadership role: Japan Breast Cancer Research Group Association (JBCRG); Honoraria (self): AstraZeneca; Chugai Pharma; Eisai; Lilly Japan; Pfizer; Takeda; Research grant/Funding (institution): AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Kyowa Hakko Kirin; Lilly; MSD; Novartis; Pfizer. E. Gokmen: Honoraria (self): Eli Lilly; Janssen Oncology; Novartis; Pfizer; Roche; Advisory/Consultancy: Lilly; Novartis; Pfizer; Roche; Speaker Bureau/Expert testimony: Lilly; Novartis; Pfizer; Roche; Travel/Accommodation/Expenses: BMS; MSD Oncology; Novartis; Pfizer; Roche. S. Loi: Advisory/Consultancy: Aduro Biotech; AstraZeneca/MedImmune; Bristol-Myers Squibb; G1 Therapeutics; Merck Sharp & Dohme; Novartis; Pfizer; Roche/Genentech; Seattle Genetics; Research grant/Funding (institution): Bristol-Myers Squibb; Lilly; Merck; Novartis; Puma Biotechnology; Roche/Genentech; Seattle Genetics. Z. Guo: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.; Shareholder/Stockholder/Stock options: Genmab (I). E. Jensen: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. G. Aktan: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. V. Karantza: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P. Schmid: Full/Part-time employment: Genentech; Roche; Honoraria (self): AstraZeneca; Novartis; Pfizer; Roche; Advisory/Consultancy: AstraZeneca; Bayer; Boehringer Ingelheim; Celgene; Eisai; Genentech/Roche; Merck; Novartis; Pfizer; Puma Biotechnology; Research grant/Funding (institution): Astellas Pharma; AstraZeneca; Genentech; Novartis; Oncogenex; Roche. J. Cortes: Shareholder/Stockholder/Stock options: MedSIR; Honoraria (self): Celgene; Daiichi Sankyo; Eisai; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Samsung; Advisory/Consultancy: AstraZeneca; Athenex; Bioasis; Biothera; Celgene; Cellestia Biotech; Clovis Oncology; Daiichi Sankyo; Erytech Pharma; GlaxoSmithKline; Leuko; Lilly; Merck Sharp & Dohme; Merus; Polyphor; Roche; Seattle Genetics; Servier; Research grant/Funding (institution): ARIAD; AstraZeneca; Baxalta GMBH/Servier Affaires; Bayer; Eisai Farmaceutica; Guardant Health; Merck Sharp & Dohme; Pfizer; Piqur; Puma CO; Queen Mary University of London; Roche; Travel/Accommodation/Expenses: Daiichi Sankyo; Eisai; Novartis; Pfizer; Roche. All other authors have declared no conflicts of interest.