Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session - Breast cancer, metastatic

LBA16 - KEYNOTE-355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC

Date

19 Sep 2021

Session

Proffered Paper session - Breast cancer, metastatic

Presenters

Hope Rugo

Citation

Annals of Oncology (2021) 32 (suppl_5): S1283-S1346. 10.1016/annonc/annonc741

Authors

H.S. Rugo1, J. Cortés2, D.W. Cescon3, S. Im4, M. Md Yusof5, C. Gallardo6, O. Lipatov7, C.H. Barrios8, J. Perez-Garcia9, H. Iwata10, N. Masuda11, M. Torregroza Otero12, E. Gokmen13, S. Loi14, Z. Guo15, X. Zhou15, V. Karantza15, W. Pan15, P. Schmid16

Author affiliations

  • 1 Department Of Hematology/oncology, University of California San Francisco Comprehensive Cancer Center, 94115 - San Francisco/US
  • 2 International Breast Cancer Center (ibcc), Quiron Group, Madrid and Barcelona, Spain; Vall d'Hebron Institute of Oncology, Barcelona, Spain; Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, 28670 - Madrid/ES
  • 3 Princess Margaret Cancer Centre, University of Toronto, M5G 1Z5 - Toronto/CA
  • 4 Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 5 Cancer Center, Pantai Hospital, Kuala Lumpur/MY
  • 6 Oncology Institute, Arturo Lopez Perez Foundation, Santiago/CL
  • 7 Department Of Oncology, Republican Clinical Oncology Dispensary, Republic of Bashkortostan/RU
  • 8 Oncology Research Unit, Hospital São Lucas, PUCRS, Porto Alegre/BR
  • 9 International Breast Cancer Center (ibcc), Quiron Group, Barcelona/ES
  • 10 Department Of Breast Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 11 Department Of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, 540-0006 - Osaka/JP
  • 12 Hematology & Oncology, Oncomedica S.A., Monteria/CO
  • 13 Medical Faculty, Ege University Medical School, 35100 - Izmir/TR
  • 14 Division Of Cancer Research, Peter Maccallum Cancer Centre, Melbourne, Australia; The Sir Peter Maccallum Department Of Medical Oncology, University of Melbourne, Parkville/AU
  • 15 Merck Research Laboratories, Merck & Co., Inc., Kenilworth/US
  • 16 Barts Cancer Institute, Centre for Experimental Cancer Medicine, EC1M 6BQ - London/GB
More

Resources

Login to access the resources on OncologyPRO.

Abstract LBA16

Background

A prior interim analysis of KEYNOTE-355 (NCT02819518) showed that first-line pembrolizumab (pembro) + chemotherapy (chemo) significantly improved PFS vs placebo (pbo) + chemo in patients (pts) with metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10) (HR, 0.65, 95% CI, 0.49–0.86; one-sided P=0.0012 [P-value boundary, 0.00411]). We present final results for the dual primary endpoint of OS and other study endpoints.

Methods

847 pts with de novo metastasis or ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane or gemcitabine-carboplatin), PD-L1 status (CPS ≥1 or <1) and prior (neo)adjuvant treatment with same-class chemo (yes or no). Dual primary endpoints are PFS (RECIST v1.1 by BICR) and OS in pts with PD-L1+ tumors (CPS ≥10 and ≥1) and all pts (ITT). ORR is a secondary endpoint. AEs were monitored throughout the study and graded per NCI CTCAE v4.0.

Results

As of June 15, 2021, median follow-up was 44.1 mo. Pembro + chemo significantly improved OS vs chemo alone in pts with CPS ≥10 tumors (Table). The p-value boundary for a significant OS benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed. The benefit of pembro + chemo on PFS was consistent with the prior results. Pembro + chemo improved ORR in pts with CPS ≥10 tumors. For all endpoints, the pembro treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths).

Conclusions

Pembro + chemo showed a statistically significant and clinically meaningful improvement in OS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). No new safety signals were identified. Table: LBA16

CPS ≥10 CPS ≥1 ITT
P + Cn = 220 Cn = 103 P + Cn = 425 Cn = 211 P + Cn = 566 Cn = 281
OS, mo, mediana (95% CI)
23.0 (19.0 – 26.3) 16.1 (12.6 – 18.8) 17.6 (15.5 – 19.5) 16.0 (12.8 – 17.4) 17.2 (15.3 – 19.0) 15.5 (13.9 – 17.2)
OS, HRb (95% CI) 0.73c (0.55 – 0.95) 0.86d (0.72 – 1.04) 0.89 (0.76 – 1.05)
PFS, mo, mediana (95% CI) 9.7 (7.6 – 11.3) 5.6 (5.3 – 7.5) 7.6 (6.6 – 8.0) 5.6 (5.4 – 7.4) 7.5 (6.3 – 7.7) 5.6 (5.4 – 7.2)
PFS, HRb (95% CI) 0.66 (0.50 – 0.88) 0.75 0.62 – 0.91 0.82 0.70 – 0.98
ORR, %(95% CI) 52.7 (45.9 – 59.5) 40.8 (31.2 – 50.9) 44.9 (40.1 – 49.8) 38.9 (32.2 – 45.8) 40.8 (36.7 – 45.0) 37.0 (31.4 – 42.9)

aFrom Kaplan-Meier method.bFrom a stratified Cox model.c P=0.0093; boundary of P=0.0113 met.d P=0.0563; boundary of P=0.0172 not met.

Clinical trial identification

NCT02819518.

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

J. Cortés: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Celestial; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Biothera Pharmaceutical; Financial Interests, Personal, Advisory Role: Merus; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Erytech; Financial Interests, Personal, Advisory Role: Athenex; Financial Interests, Personal, Advisory Role: Polyphor; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Leuko; Financial Interests, Personal, Advisory Role: Bioasis; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Kyowa Kirin; Financial Interests, Personal, Advisory Role: 4D Pharma PLC; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Celgene; Financial Interests, Personal, Funding: Eisai; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: Samsung Bioepis; Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Funding: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer Healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: F. Hoffmann-La Roche; Financial Interests, Institutional, Research Grant: Guardanth Health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma C; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Eisai; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Daiichi Sankyo. D.W. Cescon: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Non-Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Financial Interests, Personal, Principal Investigator: GlaxoSmithKline, Merck, Pfizer, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Dynamo Therapeutics, Exact Sciences, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer, Puma Biotechnology, Roche. H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Merck, Novartis, Lilly, Roche, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Ayala, Gilead; Financial Interests, Personal, Other, Honoraria: Puma, Mylan, Samsung. S. Im: Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Personal, Member of the Board of Directors: Translational Research in Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca, Daewoong, Eisai, Pfizer, Roche; Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Daichi Sankyo, Eli Lilly, Eisai, GSK, Hanmi, MSD, Novartis, Pfizer, Roche. M. Md Yusof: Non-Financial Interests, Personal and Institutional, Invited Speaker: Eli Lily, Roche, Novartis, MSD, AstraZeneca, Eisai, MSD, Zuellig Pharma, GSK, Mundi Pharma; Financial Interests, Institutional, Funding: Mundi Pharma; Financial Interests, Institutional, Principal Investigator: MSD, Novartis, Genentech, Astella, AstraZeneca; Non-Financial Interests, Personal and Institutional, Advisory Role: Eli Lily, Roche, Novartis, MSD, AstraZeneca, Eisai, MSD, Zuellig Pharma, GSK, Mundi Pharma; Non-Financial Interests, Personal, Leadership Role: Malaysian Oncological Society. C. Gallardo: Non-Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD, Roche, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca, Novartis; Financial Interests, Institutional, Principal Investigator: MSD, BMS, AstraZeneca. C.H. Barrios: Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Stocks/Shares: Biomarker, Tummi, MEDSir; Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, BioMarin, Bristol Myers Squibb, Daiichi Sankyo, Abraxis Biosciences, AB Sc; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi. J. Perez-Garcia: Financial Interests, Personal, Advisory Board: Roche, Lilly, Daichii Sankyo, AstraZeneca. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD; Financial Interests, Institutional, Funding: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD, Sanofi, Novartis, Bayer, Nihon kayaku, Boehringer Ingelheim; Non-Financial Interests, Personal, Principal Investigator: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD, Sanofi, Novartis, Bayer, Nihon kayaku, Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD. N. Masuda: Financial Interests, Personal, Speaker’s Bureau: Chugai, AstraZeneca, Pfizer, Eli-Lilly, Eisai; Non-Financial Interests, Personal, Member of the Board of Directors: JBCS (Japanese Breast Cancer Society), JBCRG (Japan Breast Cancer Research Group Association); Financial Interests, Institutional, Research Grant: Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli-Lilly, Eisai, Sanofi, Daiichi Sankyo. E. Gokmen: Financial Interests, Personal and Institutional, Invited Speaker: Roche, Pfizer, BMS, Astellas, AstraZeneca, GEN, Amgen, Novartis; Financial Interests, Personal, Advisory Board: Roche, Pfizer, BMS, AstraZeneca, Novartis, GEN; Financial Interests, Personal, Stocks/Shares: Radius Health, Immunogen, 9 Meters. S. Loi: Non-Financial Interests, Personal, Expert Testimony: Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Roche-Genentech; Financial Interests, Institutional, Expert Testimony: Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca , Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Bristol Meyers Squibb; Financial Interests, Personal, Advisory Board: Akamara Therapeutics; Financial Interests, Institutional, Research Grant: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics AstraZeneca , Roche-Genentech, Seattle Genetics. Z. Guo: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. X. Zhou: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. V. Karantza: 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. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer, Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Personal, Full or part-time Employment, Spouse: Roche; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings