43O - Phase III KEYNOTE-355 study of pembrolizumab (pembro) vs placebo (pbo) + chemotherapy (chemo) for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC): Results for patients (Pts) enrolled in Asia

Background

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.

Methods

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.

Results

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).

Conclusions

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. Table: 43O

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).

Clinical trial identification

NCT02819518.

Editorial acknowledgement

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.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

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.