KEYNOTE-119: Phase 3 study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple-negative breast cancer (mTNBC)

Date

28 Sep 2019

Session

Proffered Paper - Breast cancer, metastatic

Presenters

Javier Cortés

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

J. Cortés1, O. Lipatov2, S. Im3, A. Gonçalves4, K.S. Lee5, P. Schmid6, K. Tamura7, L. Testa8, I. Witzel9, S. Ohtani10, S. Zambelli11, N. Harbeck12, F. André13, R. Dent14, X. Zhou15, V. Karantza16, J.A. Mejia17, E.P. Winer18

Author affiliations

  • 1 Oncology, IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona; Vall d´Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 2 Medical Oncology, Republican Clinical Oncology Dispensary, 450054 - Ufa/RU
  • 3 Internal Medicine, Seoul National University, 08826 - Seoul/KR
  • 4 Medical Oncology, Institut Paoli-Calmettes, 13009 - Marseille/FR
  • 5 Center For Breast Cancer, National Cancer Center, 10408 - Goyang/KR
  • 6 Centre For Experimental Cancer Medicine, St. Barts Cancer Institute, W4 5NG - London/GB
  • 7 Department Of Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 8 Medical Oncology, Instituto do Cancer do Estado de São Paulo do Hospital das Clinicas da Faculdade de Medicina de Universidade de São Paulo, 05415-0503 - Sao Paulo/BR
  • 9 Gynaecology, University Medical Center, 20246 - Hamburg/DE
  • 10 Surgical Oncology, Hiroshima City Hiroshima Citizens Hospital, 730-85181 - Hiroshima/JP
  • 11 Medical Oncology, IRCCS Ospedale San Raffaele, 20132 - Milan/IT
  • 12 Breast Center, University of Munich (LMU), 81377 - Munich/DE
  • 13 Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 14 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 15 Biostatistics, Merck & Co., Inc., 19454 - North Wales/US
  • 16 Oncology, Merck & Co., Inc., 07065 - Rahway/US
  • 17 Breast Medical Oncology, Merck & Co., Inc., 19454 - North Wales/US
  • 18 Division Of Breast Oncology, Dana-Farber Cancer Institute, 02115 - Boston/US
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Background

Pembro showed promising antitumor activity and manageable safety in mTNBC in KEYNOTE-012 and 086. KEYNOTE-119 (NCT02555657) is a randomized, open-label phase III study of pembro monotherapy vs single-agent chemo in participants (pts) with previously treated mTNBC.

Methods

Pts with centrally confirmed TNBC, 1-2 prior systemic treatments for mTNBC, PD on latest therapy and a prior anthracycline or taxane were randomized 1:1 to pembro 200 mg Q3W or physician’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine (60% enrollment cap for each). Pts were stratified by PD-L1 + vs - and prior (neo)adjuvant therapy vs mTNBC at first diagnosis. Primary end points were OS in pts with PD-L1 combined positive score (CPS) ≥10, pts with CPS ≥1, and all pts. Secondary end points were PFS, ORR, DOR, DCR and safety. OS superiority of pembro vs chemo was tested in all pts only if superiority was shown in pts with CPS ≥1.

Results

As of 11 APR 2019, median follow-up was 9.9 mo for pembro (n = 312) and 10.9 mo for chemo (n = 310). Pembro did not significantly improve OS in pts with CPS ≥10 (P = .0574) or CPS ≥1 (P = .0728) or in all pts, although the pembro treatment effect increased as CPS increased (HR 0.78, 0.86, and 0.97, respectively; Table); in an exploratory analysis of pts with CPS ≥20, median OS was 14.9 mo with pembro vs 12.5 mo with chemo (HR 0.58, 95% CI 0.38-0.88). Pembro did not improve PFS (Table). DOR was longer with pembro vs chemo (Table). Grade 3-5 treatment-related AE rates were 14% with pembro (1 death) vs 36% with chemo (2 deaths). Rates of grade 3-4 immune-mediated AEs and infusion reactions were 3.2% vs 1.0%, with no deaths.Table:

LBA21

CPS ≥10CPS ≥1Total
PembroChemoPembroChemoPembroChemo
n = 96n = 98n = 203n = 202n = 312n = 310
OS, mo, median12.711.610.710.29.910.8
(95% CI)(9.9-16.3)(8.3-13.7)(9.3-12.5)(7.9-12.6)(8.3-11.4)(9.1-12.6)
OS, HR0.780.860.97
(95% CI)(0.57-1.06)(0.69-1.06)(0.82-1.15)
PFS, mo, median2.13.42.13.12.13.3
(95% CI)(2.0-2.5)(2.3-4.1)(2.0-2.1)(2.3-4.0)(2.0-2.1)(2.7-4.0)
PFS, HR1.141.351.60
(95% CI)(0.82-1.59)(1.08-1.68)(1.33-1.92)
ORR, %17.79.212.39.49.610.6
(95% CI)(10.7-26.8)(4.3-16.7)(8.1-17.6)(5.8-14.3)(6.6-13.4)(7.4-14.6)
DOR, mo, medianNR7.112.26.512.28.3
(range)(2.2-32.5+)(3.8-25.9+)(2.2-32.5+)(2.1+-33.0+)(2.2-32.5+)(2.1+-33.0+)
DCR, %19.817.314.315.812.218.7
(95% CI)(12.4-29.2)(10.4-26.3)(9.8-19.9)(11.1-21.6)(8.8-16.3)(14.5-23.5)

Conclusions

Pembro monotherapy did not significantly improve OS as 2/3L treatment for mTNBC vs chemo, although the pembro treatment effect increased as PD-L1 enrichment increased. Pembro was generally well tolerated and had less high-grade toxicity than chemo.

Clinical trial identification

NCT02555657.

Editorial acknowledgement

Writing assistance was provided by Christine McCrary Sisk and 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

J. Cortés: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Samsung; Advisory / Consultancy: Cellestia; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Biothera Pharmaceutical; Advisory / Consultancy: Merus; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Erytech; Advisory / Consultancy: Athenex; Research grant / Funding (institution): Ariad Pharmaceuticals; Research grant / Funding (institution): Baxalta; Research grant / Funding (institution): GMBH/Servier Affaires; Research grant / Funding (institution): Bayer Healthcare; Research grant / Funding (institution): F. Hoffman-La Roche; Research grant / Funding (institution): Guardanth Health; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Piqor Therapeutics; Research grant / Funding (institution): Puma C; Research grant / Funding (institution): Queen Mary University of London; Shareholder / Stockholder / Stock options: MedSIR. S. Im: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Ildong; Advisory / Consultancy: MediPactor; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Roche. A. Gonçalves: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Celgene. K.S. Lee: Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Research grant / Funding (institution), (support of drug): Dong-A Pharm. P. Schmid: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AZ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: BI; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Esai; Honoraria (self), Advisory / Consultancy: Puma; Honoraria (self), Advisory / Consultancy: Celgene; Research grant / Funding (institution): Genetech; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Astellas; Spouse / Financial dependant, Spouse is a consultant for Genetech/Roche: Genetech/Roche. K. Tamura: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Cyugai; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Eli Lilly; Research grant / Funding (self), Research grant / Funding (institution): Daiich-Sankyo; Research grant / Funding (self), Research grant / Funding (institution): MSD; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self), Research grant / Funding (institution): Ono; Research grant / Funding (self), Research grant / Funding (institution): Kyowa Hakko; Research grant / Funding (self), Research grant / Funding (institution): Novartis; Research grant / Funding (self), Research grant / Funding (institution): Clovis; Research grant / Funding (self), Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Taiho. L. Testa: Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche; Travel / Accommodation / Expenses: Libbs; Travel / Accommodation / Expenses: Pfizer. I. Witzel: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Daichi Sankyo; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Hexal Biosimilars; Research grant / Funding (institution): MSD. S. Ohtani: Honoraria (institution): Chugai; Honoraria (institution): Eizai; Honoraria (institution): Pfizer; Honoraria (institution): AstraZeneca. N. Harbeck: Advisory / Consultancy: Agendia; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Daiichi Sankyo; Advisory / Consultancy: Genomic Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Odonate; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Sandoz/Hexal; Advisory / Consultancy: Seattle Genetics; Speaker Bureau / Expert testimony: Nanostring; Shareholder / Stockholder / Stock options, Spouse / Financial dependant, Co-director of West German Study Group (self): West German Study Group; Full / Part-time employment: LMU Munich. F. André: Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Daiichi; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: GlaxoSmithKline. R. Dent: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. X. Zhou: Full / Part-time employment: Merck & Co., Inc.. V. Karantza: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. J.A. Mejia: Full / Part-time employment: Merck & Co., Inc.. E.P. Winer: Advisory / Consultancy: Genentech, Lilly, Carrick Therapeutics, GSK, Seattle Genetics, LEAP. All other authors have declared no conflicts of interest.

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