Background

In the phase III KEYNOTE-355 study (NCT02819518), first-line treatment with pembro + chemo resulted in statistically significant and clinically meaningful improvements in PFS and OS versus placebo + chemo in patients (pts) with advanced TNBC with PD-L1 combined positive score (CPS) ≥10. We report efficacy outcomes from the KEYNOTE-355 final analysis for pts who had disease control and discontinued chemo before pembro and for pts who experienced immune-mediated AEs.

Methods

Pts with untreated locally recurrent inoperable or metastatic TNBC were randomized 2:1 to pembro (200 mg Q3W) or placebo for 35 cycles in combination with chemo (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). Treatment continued until progression, intolerable toxicity, or (for pembro/placebo) completion of 35 cycles; pts could discontinue chemo independently of pembro/placebo (and vice versa). In this analysis, PFS per RECIST v1.1 by BICR and OS were evaluated in (a) pts who received pembro + chemo, achieved a best objective response of CR, PR, or SD lasting ≥24 wk, and received their last dose of chemo >21 days before their last dose of pembro, and (b) pts who received pembro + chemo and experienced ≥1 immune-mediated AEs (per a list of preferred terms compiled from the CTCAE v4.0).

Results

Pts were randomized to pembro + chemo (n=566) or placebo + chemo (n=281). At data cutoff (June 15, 2021), 317 pts in the pembro + chemo group had CR, PR, or SD ≥24 wk. Among these pts, discontinutation of chemo before pembro was associated with similar efficacy to that in the overall population, irrespective of tumor PD-L1 CPS (Table). Similarly, there was evidence of antitumor activity in pts who had immune-mediated AEs, overall and by tumor PD-L1 CPS (Table).

Conclusions

In this analysis of outcomes among pts who received pembro + chemo in the KEYNOTE-355 study, there was evidence for efficacy of pembro + chemo regardless of discontinuation of chemo before pembro or occurrence of immune-mediated AEs.

Table: 191MO

Clinical trial identification

NCT02819518.

Editorial acknowledgement

Medical writing assistance was provided by Sonia Mohinta, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly, Roche/Genentech, Macrogenics, OBI, Merck, Eisai, Immunomedics, Daiichi Sankyo, Seattle Genetics, and Odonate; Financial Interests, Personal, Other, Consultant: Samsung and Puma; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and Macrogenics. D.W. Cescon: Financial Interests, Personal, Advisory Role: AstraZeneca, Exact Sciences, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer and Roche; Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer and Roche; Financial Interests, Personal, Other, member of a trial steering committee: AstraZeneca, Merck and GlaxoSmithKline. S. Im: Financial Interests, Personal, Other, Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Pfizer; Financial Interests, Personal, Other, Advisory / Consultancy: Amgen, Eisai, Hanmi, Ildong, MediPactor, Novartis, Roche. M. Md Yusof: Financial Interests, Personal, Other, Received honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, MSD, Specialised Therapeutics, Zuellig Pharma, Novartis, Pfizer, Roche, Eisai, Celgene; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Arcus, Genentech, Mundi Pharma, Novartis, Pfizer, Roche. C.E. Gallardo Araneda: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Funding: Novartis pharma SAS; Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Roche. C.H. Barrios: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Eisai Europe Ltd.; GlaxoSmithKline; Novartis pharma SAS; Pfizer Pharmaceuticals Israel; Roche/Genentech; Financial Interests, Personal, Funding: AB Science; Abraxis BioScience; Amgen; Asana Biosciences; Astellas Pharma; AstraZeneca; Biomarin; Boehringer Ingelheim; Bristol Myers Squibb; Daiichi Sankyo; Exelixis; GlaxoSmithKline; ImClone Systems; Investigator in AbbVie-sponsored cl. trials; LEO Phar. N. Turner: Financial Interests, Personal, Other, Received honoraria: Pfizer Inc.; Financial Interests, Personal, Advisory Role: Pfizer Inc.; Financial Interests, Personal, Funding: Servier, Pfizer Inc., Eil Lilly, Roche, and AstraZeneca. V. Karantza, W. Pan, Z. Guo: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. J. Cortés: Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Financial Interests, Personal, Other, Honoraria (self), Travel / Accommodation /Expenses: Novartis; Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy: Celgene; Financial Interests, Personal, Other, Honoraria (self), Advisory /Consultancy: Eisai; Financial Interests, Personal, Other, Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria (self): Samsung; Financial Interests, Personal, Other, Advisory / Consultancy: Cellestia, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Financial Interests, Institutional, Other, Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Financial Interests, Institutional, Other, Research grant / Funding (institution): Ariad Pharmaceuticals, Baxalta, GMBH/Servier Affaires, Bayer Healthcare, F. Hoffman-La Roche, Guardanth Health, Merck Sharp & Dohme, Piqor Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Shareholder / Stockholder / Stock options: MedSIR. All other authors have declared no conflicts of interest.