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Proffered Paper - GU, non prostate 1

LBA23 - Pembrolizumab (P) combined with chemotherapy (C) vs C alone as first-line (1L) therapy for advanced urothelial carcinoma (UC): KEYNOTE-361

Date

19 Sep 2020

Session

Proffered Paper - GU, non prostate 1

Presenters

Ajjai Alva

Citation

Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325

Authors

A. Alva1, T. Csőszi2, M. Ozguroglu3, N. Matsubara4, L. Geczi5, S.Y. Cheng6, Y. Fradet7, S. Oudard8, C. Vulsteke9, R. Morales Barrera10, A. Fléchon11, S. Gunduz12, Y. Loriot13, A. Rodriguez-Vida14, R. Mamtani15, E.Y. Yu16, K. Nam17, K. Imai18, B.H. Moreno19, T.B. Powles20

Author affiliations

  • 1 Hematology/oncology, University of Michigan, 48109 - Ann Arbor/US
  • 2 Oncology, Hetenyi G Korhaz Onkologiai Kozpont, Szolnok/HU
  • 3 Medical Oncology, Istanbul University- Cerrahpaşa, Cerrahpaşa School of Medicine, 35500096 - Istanbul/TR
  • 4 Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 5 Medical Oncology, National Institute of Oncology - Hungary, 1122 - Budapest/HU
  • 6 Oncology, Sunnybrook Odette Cancer Centre, Toronto/CA
  • 7 Surgery/uuology, CHU de Québec-Université Laval, G1R 3J6 - Québec City/CA
  • 8 Immunothérapie Et Traitement Antiangiogénique En Pathologie cancérologique, Hopital European George Pompidou, 75015 - Paris/FR
  • 9 Center For Oncological Research (core), Antwerp, 9000 - Antwerp/BE
  • 10 Medical Oncology Dept., Vall d'Hebron University Hospital, 8035 - Barcelona/ES
  • 11 Department Of Medical Oncology, Centre Léon Bérard, Rhones-Alpes/FR
  • 12 Medical Oncology Department, Memorial Antalya Hospital, 07020 - Antalya/TR
  • 13 Cancer Medicine Department, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 14 Medical Oncology Department, Hospital del Mar, Barcelona/ES
  • 15 Hematology/oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 16 Medicine/oncology Department, University of Washington, WA 98109 - Seattle/US
  • 17 Statistics, Merck & Co., Inc., Kenilworth/US
  • 18 Clinical Research Oncology Department-po Box 1000, Merck & Co., Inc., Kenilworth/US
  • 19 Medical Oncology, Merck & Co., Inc., 07033 - Kenilworth/US
  • 20 Medical Oncology Department, Barts Cancer Institute, Queen Mary University of London, EC1M 6BE - London/GB
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Resources

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Abstract LBA23

Background

The open-label, phase III KEYNOTE-361 study compares efficacy and safety of 1L P + C vs C for advanced UC (NCT02853305).

Methods

Eligible pts had advanced/unresectable or metastatic UC, ECOG PS 0-2, and no prior systemic therapy for advanced disease. Pts from 201 sites in 21 countries were randomized 1:1:1 to P 200 mg Q3W for ≤35 cycles, P for ≤35 cycles + C for ≤6 cycles (investigator’s choice [IC] of gemcitabine + either cisplatin or carboplatin), or IC of C for ≤6 cycles. Randomization was stratified by IC of platinum and PD-L1 combined positive score (CPS) (≥10 vs <10). Dual primary endpoints were PFS by blinded central review and OS. A sequential testing strategy was used, beginning with superiority testing of PFS and OS for P + C vs C in the total population (P-value threshold of ≤0.0019 for PFS and ≤0.0142 for OS as adjusted for α spent at interim analyses to maintain overall α=2.5% [one-sided] with 0.5% and 2.0% allocated to PFS and OS, respectively), followed by noninferiority and superiority testing of OS for P vs C in pts with CPS≥10 and total pts only if OS for P + C was statistically superior to C.

Results

1010 pts were randomized between Oct 19, 2016 and Jun 29, 2018: 351 to P + C, 307 to P, and 352 to C. As of Apr 29, 2020, median (range) time from randomization to cutoff was 31.7 (22.0-42.3) mo. Baseline characteristics were generally well-balanced across arms. Median PFS for P + C, P, and C for total pts was 8.3 mo, 3.9 mo, and 7.1 mo, respectively; median OS was 17.0 mo, 15.6 mo, and 14.3 mo, respectively. HR (95% CI) for P + C vs C was 0.78 (0.65-0.93, P = 0.0033) for PFS and 0.86 (0.72-1.02, P = 0.0407) for OS. ORR was 54.7% for P + C, 30.3% for P, and 44.9% for C. Median DOR (range) was 8.5 (2.0+-35.5+) mo, 28.2 (2.1+-36.1+) mo, and 6.2 (1.8+-36.3+) mo, respectively. 35.3%, 41.0%, and 61.1% of total pts in P+C, P, and C arms received subsequent therapy (6.6%, 4.6%, and 48.0% of total pts received anti–PD-[L]1), respectively. Grade 3-5 TRAE rate was 75.1% with P + C, 16.9% with P, and 71.6% with C; discontinuation rate of any drug due to an AE was 30.9%, 15.9%, and 18.1%, respectively.

Conclusions

PFS and OS benefit upon addition of P to C vs C did not reach statistical significance. Due to statistical design, OS noninferiority/superiority of P vs C was not tested.

Clinical trial identification

NCT02853305, August 2, 2016.

Editorial acknowledgement

Ina Nikolaeva of 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

A. Alva: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: EMD Serono; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Progenics; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Esanik; Research grant/Funding (institution): Ionis; Research grant/Funding (institution): Argus Biosciences; Research grant/Funding (institution): Prometheus; Full/Part-time employment: University of Michigan. T. Csőszi: Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. M. Ozguroglu: Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. N. Matsubara: Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): MSD, a subsidiary of Merck & Co., Inc.; Advisory/Consultancy, Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Chigai; Advisory/Consultancy: Sanofi. L. Geczi: Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. S.Y-S. Cheng: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca. Y. Fradet: Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tersera; Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Astellas. S. Oudard: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Merck & Co., Inc.; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Research grant/Funding (self): Ipsen; Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. C. Vulsteke: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Honoraria (self): Janssen; Honoraria (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution): Leo Pharma; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Astellas; Travel/Accommodation/Expenses: Novartis. R. Morales Barrera: Honoraria (self), Advisory/Consultancy: Sanofi Aventis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD, a subsidiary of Merck & Co., Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Asofarma; Travel/Accommodation/Expenses: Pharmacyclics; Travel/Accommodation/Expenses: Clovis; Travel/Accommodation/Expenses: Lilly. A. Fléchon: Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca. S. Gunduz: Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Y. Loriot: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Astellas; Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self): Seattle Genetics; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (self): Ipsen. A. Rodriguez-Vida: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Sanofi-Aventis; Advisory/Consultancy: Clovis; Research grant/Funding (institution): Takeda. R. Mamtani: Honoraria (self): Med Learning Group; Advisory/Consultancy: Flatiron Health; Advisory/Consultancy: Roche/Genetech; Advisory/Consultancy: Seattle Genetics/Astellas; Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. E.Y. Yu: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Advanced Accelerator Applications; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Clovis; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Blue Earth; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Dendreon; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Taiho. K. Nam: Full/Part-time employment: Merck & Co., Inc. K. Imai: Full/Part-time employment: Merck & C., Inc. B.H. Moreno: Full/Part-time employment: Merck & Co., Inc. T.B. Powles: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: BMS; Honoraria (institution), Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Ipsen; Honoraria (institution), Advisory/Consultancy: MSD, a subsidiary of Merck & Co., Inc.; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche.

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