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Virtual Plenary Debate

VP7_2021 - KEYNOTE-522: Phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer (TNBC)

Date

17 Sep 2021

Session

Virtual Plenary Debate

Presenters

Peter Schmid

Authors

P. Schmid

Author affiliations

  • Centre Of Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
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Resources

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Abstract

Abstract

P. Schmid1, J. Cortes2, R. Dent3, L. Pusztai4, H. McArthur5, S. Kümmel6, J. Bergh7, C. Denkert8, Y.H. Park9, R. Hui10, N. Harbeck11, M. Takahashi12, M. Untch13, P.A. Fasching14, F. Cardoso15, Y. Ding16, K. Tryfonidis17, G. Aktan17, V. Karantza17, J. O’Shaughnessy18
1Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University London, London, UK, 2International Breast Cancer Center, Quirón Group, Madrid and Barcelona, Spain, and Vall d'Hebron Institute of Oncology, Barcelona, Spain, 3National Cancer Center Singapore, Duke–National University of Singapore Medical School, Singapore, 4Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA, 5Breast Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA, 6Breast Unit, Kliniken Essen-Mitte, Essen, Germany, 7Department of Oncology-Pathology, Karolinska Institutet and Breast Cancer Centre, Cancer Theme, Karolinska University Hospital, Solna, Sweden, 8Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Marburg, Germany, 9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 10Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney, Sydney, NSW, Australia, 11Breast Center, LMU University Hospital, Munich, Germany, 12Department of Breast Surgery, Hokkaido Cancer Center, Sapporo, Japan, 13Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin, Germany, 14University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany, 15Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal, 16Biostatistics, Merck & Co., Inc., Kenilworth, NJ, USA, 17Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ, USA, 18Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA

Background: KEYNOTE-522 (NCT03036488) is a phase III study of neoadjuvant pembrolizumab (pembro) + chemotherapy (chemo) vs. placebo (pbo) + chemo followed by adjuvant pembro vs. pbo in patients (pts) with early-stage TNBC. In prior interim analyses, pembro + chemo showed a significant improvement in pCR and a favorable trend in EFS. We present results from a prespecified interim analysis of KEYNOTE-522.

Methods: 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 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. Pts were stratified by nodal status (+ vs. -), tumor size (T1/T2 vs. T3/T4), and carboplatin schedule (Q3W vs. QW). Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS.

Results: 1174 pts were randomized to pembro (n=784) or pbo (n=390). At the March 23, 2021 data cutoff (median follow-up, 37.8 mo [range, 2.7-48.0]), 123 pts (15.7%) in the pembro group and 93 pts (23.8%) in the pbo group had an EFS event, defined as disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR 0.63 [95% CI, 0.48-0.82]; P=0.0003). The 36-mo EFS rate was 84.5% (95% CI, 81.7-86.9) in the pembro group vs. 76.8% (95% CI, 72.2-80.7) in the pbo group; median was not reached in either group. The most common EFS event was distant recurrence, in 60 pts (7.7%) in the pembro group vs. 51 pts (13.1%) in the pbo group. Pembro showed a favorable trend in OS (HR 0.72 [95% CI, 0.51-1.02]); follow-up is ongoing. Grade ≥3 treatment-related AE rates were 77.1% in the pembro group and 73.3% in the pbo group (death incidence, 0.5% vs. 0.3%, respectively); immune-mediated AEs of any grade occurred in 43.6% vs. 21.9%, respectively.

Conclusions: Neoadjuvant pembro + chemo followed by adjuvant pembro showed a statistically significant and clinically meaningful improvement in EFS compared with neoadjuvant chemotherapy alone in pts with early-stage TNBC.

Clinical trial identification: NCT03036488.

Editorial acknowledgement: Medical writing and/or editorial assistance was provided by Christine McCrary Sisk. 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: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure:
P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca; Bayer; Boehringer Ingelheim; Merck; Novartis; Pfizer; Puma; Roche; Eisai; Celgene; Financial Interests, Personal, Other, Spouse: Roche; Financial Interests, Institutional, Research Grant: Astellas; AstraZeneca; Genentech; Novartis; Oncogenex; Roche; Medivation.
J. Cortes: Financial Interests, Personal, Invited Speaker: Roche; Novartis; Celgene; Eisai; Pfizer; Samsung Bioepis; Lilly; Merck Sharp & Dohme; Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche; Celgene; Cellestia; AstraZeneca; Biothera Pharmaceutical; Merus; Seattle Genetics; Daiichi Sankyo; Erytech; Athenex; Polyphor; Lilly; Servier; Merck Sharp & Dohme; GSK; Leuko; Bioasis; Clovis Oncology; Boehringer Ingelheim; Kyowa Kirin; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche; Ariad Pharmaceuticals; AstraZeneca; Baxalta GMBH/Servier Affaires; Bayer Healthcare; Merck Sharp & Dohme; Pfizer; Piqur Therapeutics; Puma C; Queen Mary University of London; F. Hoffman-La Roche; Guardant Health; Eisai; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche; Novartis; Eisai; Pfizer; Daiichi Sankyo.
R. Dent: Financial Interests, Personal, Advisory Board: AstraZeneca; Eisai; Eli Lilly; Genentech; Merck; Novartis; Pfizer; Financial Interests, Personal, Other, Consultant: Genentech; Financial Interests, Personal, Other, Travel expenses: Genentech; Merck; Pfizer.
L. Pusztai: Financial Interests, Personal, Advisory Board: Seagen; Pfizer; AstraZeneca; Merck; Novartis; Bristol-Myers Squibb; Genentech; Eisai; Pieris; Immunomedics; Clovis; Syndax; H3Bio; Radius Health; Daiichi; Non-Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Non-Financial Interests, Institutional, Principal Investigator: Merck; Pfizer; AstraZeneca; Seagen.
H. McArthur: Financial Interests, Personal, Advisory Board: Amgen; Bristol-Myers Squibb; Eli Lilly; Genentech/Roche; Immunomedics; Merck; Pfizer; Puma; Daiichi Sankyo; Seattle Genetics; AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; MedImmune; AstraZeneca; BTG; Merck.
S. Kümmel: Financial Interests, Personal and Institutional, Invited Speaker: Roche; Genomic Health; Exact Science; Seagen; Novartis; Amgen; Celgene; Daiichi Sankyo; AstraZeneca; Somatex/Hologic; MSD; Pfizer; PFM Medical; Lilly; Financial Interests, Personal and Institutional, Advisory Board: Roche; Genomic Health; Exact Science; Seagen; Novartis; Amgen; Celgene; Daiichi Sankyo; AstraZeneca; Somatex/Hologic; MSD; Pfizer; PFM Medical; Lilly; Non-Financial Interests, Personal, Member of the Board of Directors: WSG - Westdeutsche Studiengruppe - co Director; Financial Interests, Institutional, Research Grant: Somatex/Hologic; Financial Interests, Personal and Institutional, Principal Investigator: Roche; Novartis; Somatex/Hologic; Non-Financial Interests, Personal, Member: ESMO; ASCO; DGS; DGGG; WSG; AGO; AGImed; Non-Financial Interests, Personal, Member of the Board of Directors: AGO.
J. Bergh: Other, Institutional, Invited Speaker, Agreement with Karolinska Institutet: AstraZeneca; Roche; Non-Financial Interests, Institutional, Member of the Board of Directors: Karolinska Comprehensive Cancer Center; Cancer Core Europe; Cancer Research Karolinska Institutet; Financial Interests, Personal, Full or part-time Employment: Karolinska Institutet; Karolinska University Hospital, Karolinska CCC; Financial Interests, Personal and Institutional, Ownership Interest: Asklepios Medicin HB; Financial Interests, Institutional, Royalties, For participation in writing for UpToDate: Asklepios Medicin HB; Financial Interests, Institutional, Research Grant, Prior to last 3 years: AstraZeneca; Amgen; Bayer; Merck; Pfizer; Roche; Sanofi-Aventis; Financial Interests, Institutional, Funding: Swedish Cancer Society; Cancer Society in Stockholm; Knut and Alice Wallenberg Society; Swedish Research Council; Financial Interests, Institutional, Principal Investigator: Prospective academic studies; Non-Financial Interests, Personal and Institutional, Member: ASCO; AACR; ESMO; Nobel Assembly; Non-Financial Interests, Personal and Institutional, Member, Founding member: ECCO Academy; Non-Financial Interests, Personal and Institutional, Member, Fellow: Royal College of Physicians; Non-Financial Interests, Personal and Institutional, Member, Adjunct member: Nobel Committee; Non-Financial Interests, Personal and Institutional, Affiliate, Visiting Professor: Oxford University; Non-Financial Interests, Personal and Institutional, Advisory Role: European Medicines Agency; Swedish Medicine Products Agency; Non-Financial Interests, Institutional, Leadership Role: Cancer Research KI.
C. Denkert: Financial Interests, Personal, Advisory Board, (Oncology): MSD; Daiichi Sankyo; Molecular Health; AstraZeneca; Merck; Novartis; Roche; Financial Interests, Personal, Ownership Interest, (until 2016): Sividon Diagnostics; Financial Interests, Personal, Royalties: VMscope digital pathology software; Financial Interests, Institutional, Funding: Myriad; Roche; GBG.
Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Pfizer; Roche; Novartis; Merck; Financial Interests, Institutional, Research Grant: AstraZeneca; Pfizer; Roche; Merck; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Pfizer; Roche; Daiichi Sankyo; Novartis; Merck; Financial Interests, Personal, Other, Speaker fee: Roche; Novartis; Non-Financial Interests, Personal, Other, Medical writing support: F. Hoffmann-La Roche Ltd.
R. Hui: Financial Interests, Personal, Invited Speaker: MSD; Novartis; AstraZeneca; Roche; Non-Financial Interests, Personal, Writing Engagements: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; BMS; Eli Lilly; Merck; MSD; Novartis; Oncosec; Pfizer; Roche; Seagen.
N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca; Daiichi Sankyo; Lilly; MSD; Novartis; Pfizer; Pierre Fabre; Roche; Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca; Daiichi Sankyo; Lilly; MSD; Novartis; Pfizer; Pierre Fabre; Roche; Sandoz/Hexal; Seagen; Non-Financial Interests, Personal, Officer: ESMO Guideline Committee; Financial Interests, Personal, Full or part-time Employment: LMU University Hospital; Financial Interests, Personal, Ownership Interest: WSG; Non-Financial Interests, Personal, Member: AGO, Germany; ESO/ESCO.
M. Takahashi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Eli Lilly; Eisai; Pfizer.
M. Untch: Financial Interests, Institutional, Invited Speaker: AstraZeneca; Celgene; Amgen; Pfizer; Roche; Lilly; Daiichi Sankyo; Mylan; Novartis; MSD; Seagen; Pierre Fabre; GSK; Financial Interests, Personal, Writing Engagements: AstraZeneca GmbH; Daiichi Sankyo; Exact Sciences Deutschland; Lilly; Mylan Germany; Pierre Fabre; Veracyte, Inc; Financial Interests, Institutional, Advisory Board: AbbVie; AstraZeneca; Celgene; Amgen; Pfizer; Roche; Lilly; GSK; Daiichi Sankyo; Novartis; MSD; Seagen; Celgene; Pierre Fabre; Agendia; Mylan; Financial Interests, Institutional, Advisory Role: AbbVie; AstraZeneca; Celgene; Amgen; Pfizer; Roche; Lilly; GSK; Daiichi Sankyo; Novartis; MSD; Seagen; Pierre Fabre; Agendia.
P.A. Fasching: Financial Interests, Personal, Advisory Board: Agendia; AstraZeneca; Daiicho Sankyo; Eisai; Hecal; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; Pierre Fabre; Roche; Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Daiichi Sankyo; Eisai; Lilly; Merck Sharp & Dohme; Novartis; Seagen; Non-Financial Interests, Institutional, Principal Investigator: BionTech; Cepheid; Non-Financial Interests, Personal, Member: Arbeitsgemeinschaft für Gynäkologische Onkologie e.v.; ASCO; Deutsche Gesellschaft für Senologie e.v.; Translational Research in Oncology.
F. Cardoso: Financial Interests, Personal, Advisory Board: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi Sankyo; Eisai; GE Oncology; Genentech; GlaxoSmithKline; Macrogenics; Medscape; Merck Sharp & Dohme; Merus BV; Mundipharma; Mylan Pharmaceuticals Inc.; Novartis Pharma; Pfizer; Pierre Fabre; prIME Oncology; Roche; Samsung Bioepis; Sanofi; Seattle Genetics; Teva Pharmaceutical Industries.
Y. Ding: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.
K. Tryfonidis: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.
G. Aktan: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.
V. Karantza: 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, Speaker’s Bureau: Lilly; Pfizer; Seagen; Financial Interests, Personal, Advisory Board: AbbVie Inc.; Agendia; Amgen Biotechnology; Aptitude Health; AstraZeneca; Bayer; Bristol-Myers Squibb; Celgene Corporation; Clovis Oncology; Daiichi Sankyo; Eisai; G1 Therapeutics; Genentech; Gilead Sciences; GRAIL; Halozyme Therapeutics; Heron Therapeutics; Immunomedics; Ipsen Biopharmaceuticals; Lilly; Merck; Myriad; Nektar Therapeutics; Novartis; Pfizer; Pharmacyclics; Pierre Fabre Pharmaceuticals; Puma Biotechnology; Prime Oncology; Roche; Samsung Bioepis; Sanofi; Seagen; Syndax Pharmaceuticals; Taiho Oncology; Takeda; Synthon.


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