1O - KEYNOTE-522 Asian subgroup: Phase III study of neoadjuvant pembrolizumab (pembro) vs placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo for early triple-negative breast cancer (TNBC)

Background

In KEYNOTE-522 (NCT03036488), neoadjuvant pembro + chemo significantly increased the pathologic complete response (pCR) rate vs pbo + chemo (64.8% vs 51.2%; P<0.001) in early TNBC. We evaluated outcomes among pts enrolled in Asia.

Methods

Pts with previously untreated, nonmetastatic, centrally confirmed TNBC (T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to pembro 200 mg Q3W or pbo, both given with 4 cycles of paclitaxel + carboplatin, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide (neoadjuvant phase). After definitive surgery, pts received pembro/pbo for 9 cycles or until recurrence or unacceptable toxicity (adjuvant phase). Pts were stratified by nodal status (+ vs −), tumor size (T1/T2 vs T3/T4), and carboplatin schedule (Q3W vs QW). Primary endpoints were pCR defined as ypT0/Tis ypN0 and event-free survival. Secondary endpoints included pCR defined as ypT0 ypN0 and ypT0/Tis and OS, and all efficacy outcomes in pts with tumor PD-L1 combined positive score (CPS) ≥1. AEs were monitored until 30 days after treatment discontinuation. No alpha was assigned to this analysis.

Results

As of Sep 24, 2018, 215/1174 pts in the overall population were enrolled from Korea, Japan, Taiwan, and Singapore (pembro, n = 136; pbo, n = 79). Median age was 46 y in the pembro arm and 51 y in the pbo arm. Median follow-up was 13.0 mo. pCR rates (ypT0/Tis ypN0; primary endpoint) among the first 125 randomized pts (pembro, n = 75; pbo, n = 50) were 59% (95% CI, 47–70) with pembro vs 40% (95% CI, 26–55) with pbo (difference, 19%; 95% CI, 1–35). Results were consistent for the secondary pCR definitions, ypT0 ypN0 (51% vs 30%) and ypT0/Tis (61% vs 42%). pCR rates (ypT0/Tis ypN0) were 71% vs 63% in pts with CPS ≥10 and 51% vs 26% with CPS <10. Across both phases for all 215 pts (safety set), incidence of grade ≥3 treatment-related AEs was 75% with pembro vs 76% with pbo (no deaths for either).

Conclusions

Consistent with the overall study population, pembro + neoadjuvant chemo demonstrated clinically meaningful improvement in pCR rates in pts from Asia with early TNBC. AEs were consistent with the known safety profiles of each agent.

Clinical trial identification

NCT03036488.

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

R. Dent: Advisory/Consultancy: AstraZeneca; Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Merck; Pfizer; Roche. J. Cortes: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Pfizer; Honoraria (self): Samsung Bioepis; Honoraria (self), Advisory/Consultancy: Celgene; Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharpe & Dohme; Advisory/Consultancy: Cellestia; Biothera Pharmaceuticals; Merus; Seattle Genetics; Erytech; Athenex; Polyphor; Servier; Ariad Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Bayer Healthcare; Piqur Therapeutics; Puma C; Queen Mary University of London; Seagen; Shareholder/Stockholder/Stock options: MedSIR. L. Pusztai: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Genentech; Eisai; Pieris; Immunomedics; Almac; Syndax; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Seattle Genetics. H.L. McArthur: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Spectrum Pharm; Lilly; Amgen; Immunomedics; Pfizer; Genentech; AstraZeneca; Travel/Accommodation/Expenses: Puma Biotechnology. S. Kuemmel: Advisory/Consultancy: Roche; Genomic Health; Novartis; Amgen; Celgene; Daiichi Sankyo; AstraZeneca; Somatex; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Pfizer; PFM Medical; Lilly; Sonoscape; Research grant/Funding (institution): Roche, Somatex; Shareholder/Stockholder/Stock options, Minority Ownership Interest: WSG Study Group; Travel/Accommodation/Expenses: Roche, Daiichi Sankyo, Sonoscape. J. Bergh: Research grant/Funding (institution): Amgen; AstraZeneca; Bayer; Merck; Roche; Pfizer; Sanofi Aventis. C. Denkert: Honoraria (self): Teva; Novartis; Pfizer; Roche; Amgen; Advisory/Consultancy: Amgen; MSD; Daiichi Sankyo; Shareholder/Stockholder/Stock options: Sividon (Myriad); Licensing/Royalties: VmScope. Y.H. Park: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self): Eisai; Advisory/Consultancy, Research grant/Funding (self): Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Research grant/Funding (self): AstraZeneca. R. Hui: Honoraria (self), Advisory/Consultancy: MSD; Novartis; Roche; AstraZeneca; BMS; Eli Lilly. N. Harbeck: Advisory/Consultancy: BMS; Roche; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Speaker Bureau/Expert testimony, Fees for Non-CME Services: Roche; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Takahashi: Honoraria (self): AstraZeneca; Pfizer; Eli Lilly; Eisai; Research grant/Funding (self): Eisai; Taiho; Kyowa-Hakko Kirin; Nippon Kayaku. T. Foukakis: Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Licensing/Royalties: Wolters Kluwer Health. P.A. Fasching: Honoraria (institution): Novartis; Biontech; Cepheid; Honoraria (self): Novartis; Roche; Pfizer; Celgene; Daiichi-Sankyo; Teva; AstraZeneca; Merck Sharp & Dohme; Myelo Therapeutics; MacroGenics; Eisai; Puma; Advisory/Consultancy: Novartis; Roche; Pfizer; Celgene; Daiichi-Sankyo; Teva; AstraZeneca; Merck Sharp & Dohme; Myelo Therapeutics; MacroGenics; Eisai; Puma; Research grant/Funding (institution): Novartis; Biontech; Cepheid. F. Cardoso: Advisory/Consultancy, Research grant/Funding (institution): Amgen; AstraZeneca; Daiichi-Sankyo; Eisai; Genentech; GlaxoSmithKline; MacroGenics; MSD; Novartis; Pfizer; Pierre-Fabre; Roche; Sanofi; Advisory/Consultancy: Astellas/Medivation; Celgene; GE Oncology; Medscape; Merus BV; Mylan; Mundipharma; prIME Oncology; Seattle Genetics; Teva; Research grant/Funding (institution): Boehringer Ingelheim; Bristol-Myers Squibb; Fresenius GmbH; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Medigene; MedImmune; Millenium; Sonus; Tesaro; Tigris; Wilex; Wyeth; Officer/Board of Directors: ESMO Board of Directors. L. Jia; E. Jensen; V. Karantza; G. Aktan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. J. O'Shaughnessy: Honoraria (self): AbbVie Inc; Agendia; Amgen Biotechnology; AstraZeneca; Bristol-Myers Squibb; Celgene Corporation; Eisai; Genentech; Genomic Health; GRAIL; Immunomedics; Heron Therapeutics; Ipsen Biopharmaceuticals; Jounce Therapeutics; Lilly; Merck; Myriad; Novartis; Nov. P. Schmid: Honoraria (self): Pfizer, AZ, Novartis, Roche, Merck, BI, Bayer, Eisai, Puma, Celgene; Advisory/Consultancy: Pfizer, AZ, Novartis, Roche, Merck, BI, Bayer, Eisai, Puma, Celgene; Research grant/Funding (institution): AZ, Genentech, Roche, Oncogenex, Novartis, Astellas; Spouse/Financial dependant, Spouse is a Consultant: Genentech/Roche.