LBA18 - Pembrolizumab or placebo plus chemotherapy followed by pembrolizumab or placebo for early-stage TNBC: Updated EFS results from the phase III KEYNOTE-522 study

Background

KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pCR and EFS with the addition of pembrolizumab (pembro) to chemotherapy (chemo) in patients (pts) with early-stage TNBC. Here, we present updated EFS results after ∼5 yr median follow-up.

Methods

Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause).

Results

1174 pts were randomized to pembro (n=784) or pbo (n=390). At data cutoff (March 23, 2023), median follow-up was 63.1 mo. 145 pts (18.5%) in the pembro group and 108 pts (27.7%) in the pbo group had an EFS event (HR 0.63 [95% CI, 0.49-0.81]). The 60-mo EFS rate (95% CI) was 81.3% (78.4-83.9) vs 72.3% (67.5-76.5), respectively; the median was not reached in either group. The most common first EFS event was distant recurrence, in 72 pts (9.2%) in the pembro group vs 55 pts (14.1%) in the pbo group. With 210 distant events, rates of distant disease progression- or distant recurrence-free survival at 60 mo were 84.4% with pembro vs 76.8% with pbo (HR 0.64 [95% CI, 0.49-0.84]). The EFS benefit with pembro was consistent across prespecified subgroups, including PD-L1 expression and nodal status. In a prespecified, non-randomized, exploratory analysis, 5-yr EFS rates in the pembro and pbo groups were 92.2% vs 88.2% in pts with a pCR, and 62.6% vs 52.3% in pts without a pCR. Follow-up for OS is ongoing.

Conclusions

Neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful improvement in EFS compared with neoadjuvant chemo alone in pts with early-stage TNBC, regardless of the pCR outcome.

Clinical trial identification

NCT03036488.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Disclosure

P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, Seagen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, Guardant Health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca, Steamline Therapeutics; Other, travel cost and expenses: Merck Sharp&Dhome. R.A. Dent: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Merck, Pfizer, Lilly, Novartis, Roche; Financial Interests, Personal, Other, Travel: AstraZeneca, Eisai, Merck, Pfizer, Roche. L. Pusztai: Financial Interests, Personal, Advisory Board, advisory board, trial steering committee membership: AstraZeneca; Financial Interests, Personal, Advisory Board: pfizer, roche genentech, novartis, Exact Sciences, Natera; Financial Interests, Personal, Advisory Board, advisory board, trial steering committee: Merck; Financial Interests, Personal, Advisory Board, advisory board: Biotheranostics; Financial Interests, Personal, Advisory Board, investigator meeting: Biovica; Financial Interests, Institutional, Trial Chair, clinical trial support to institution: pfizer, merck; Financial Interests, Institutional, Local PI, clinical trial support to institution: seagen, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant: bristol myers squibb; Non-Financial Interests, Advisory Role, member of the scientific advisory board: Breast Cancer Research Foundation; Non-Financial Interests, Member of Board of Directors: SWOG Hope Foundation; Non-Financial Interests, Institutional, Product Samples, material transfer agreement: pfizer. H.L. McArthur: Financial Interests, Personal, Advisory Board: Lilly, Pfizer, Immunomedics, Merck, Seattle Genetics, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Puma Biotechnology, Gilead, Crown Bioscience; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MedImmune, AstraZeneca, Merck. S. Kummel: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Stemline, Gilead, MSD; Lilly, Novartis, Pfizer, Seagen, Daiichi Sankyo, Exact Science; Financial Interests, Personal and Institutional, Advisory Board: Roche, AstraZeneca, Stemline, Gilead, MSD; Lilly, Novartis, Pfizer, Seagen, Exact Science, Daiichi Sankyo; Non-Financial Interests, Member of Board of Directors: ESMO, AGO, WSG; Non-Financial Interests, Ownership Interest: WSG; Financial Interests, Personal and Institutional, Principal Investigator, Both financial and non-financial: Roche, AstraZeneca, Stemline, Gilead, MSD; Lilly, Novartis, Pfizer, Seagen, Exact Science, Daiichi Sankyo, GSK; Non-Financial Interests, Advisory Role: ESMO, AGO, WSG; Financial Interests, Personal, Advisory Board: Novartis, MSD, Hologic, Stryker, Lilly. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Roche, Lilly, Diaceutics, VmScope digital pathology software; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, Myriad, German Breast Group. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Lilly, Pfizer, Novartis, MSD, Roche, Daiichi Sankyo; Financial Interests, Institutional, Writing Engagement: Pfizer. R. Hui: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Eisai, Merck, Oncosec, Amgen, Takeda, Zai Lab; Financial Interests, Personal, Invited Speaker: MSD, Novartis, AstraZeneca, Eli Lilly, Janssen; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Eli Lilly, Janssen, MSD, Novartis, Oncosec, Roche, Seagen, Corvus; Financial Interests, Personal, Steering Committee Member: MSD; Financial Interests, Steering Committee Member: AstraZeneca; Non-Financial Interests, Member: ASCO, IASLC, Medical Oncology Group of Australia (MOGA); Non-Financial Interests, Other, Member of IASLC Education Committee: IASLC. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. M. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Pfizer, Eisai, Daiichi Sankyo, MSD. T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Advisory Board: Affibody; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): Pfizer, AstraZeneca; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): Novartis. M.A. Mouret Reynier: Financial Interests, Personal and Institutional, Invited Speaker: Novartis, Pfizer, Lilly, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Lilly, AstraZeneca, MSD. M.I.R. Ferreira: Financial Interests, Institutional, Local PI: MSD, Taiho Oncology, AstraZeneca; Financial Interests, Institutional, Other, Sub-investigator: Daiichi Sankyo, Roche, AstraZeneca, Novartis, MSD; Non-Financial Interests, Member, Board member (treasurer) of a non-profit association that promotes knowledge in Oncology.: Grupo de Estudos Oncológicos. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, Iqvia, Touchime; Financial Interests, Institutional, Local PI: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers-Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC. Y. Ding: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. W. Pan: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. K.E. Tryfonidis: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi.