Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Pembrolizumab+Chemotherapy vs Placebo+Chemotherapy by PD-L1 combined positive score 1-9, 10-19, and ≥20 for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer: KEYNOTE-355 subgroup analysis (#217)

Sherene Loi 1 , David W. Cescon 2 , Hope S. Rugo 3 , Zbigniew Nowecki 4 , Seock-Ah Im 5 , Mastura Md Yusof 6 , Carlos Gallardo 7 , Oleg Lipatov 8 , Carlos Henrique Barrios 9 , Jose Perez-Garcia 10 , Hiroji Iwata 11 , Norikazu Masuda 12 , Marco Torregroza Otero 13 , Erhan Gokmen 14 , Zifang Guo 15 , Xuan Zhou 15 , Vassiliki Karantza 15 , Wilbur Pan 15 , Peter Schmid 16 , Javier Cortes 17 , Julia Douglas 18
  1. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; The Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, Australia
  2. Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  3. University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA
  4. Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
  5. Seoul National University Hospital, Seoul, Republic of Korea
  6. Cancer Center at Pantai Hospital, Kuala Lumpur, Malaysia
  7. Arturo Lopez Perez Foundation, Santiago, Chile
  8. Republican Clinical Oncology Dispensary, Republic of Bashkortostan, Russian Federation
  9. Oncology Research Unit, Hospital São Lucas, PUCRS, Porto Alegre, Brazil
  10. International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain
  11. Aichi Cancer Center Hospital, Nagoya, Japan
  12. Nagoya University Graduate School of Medicine, Nagoya, Japan
  13. Oncomedica S.A., Monteria, Colombia
  14. Ege University Medical School, Izmir, Turkey
  15. Merck & Co., Inc., Rahway, NJ, USA
  16. Barts Cancer Institute, Centre for Experimental Cancer Medicine, London, UK
  17. International Breast Cancer Center (IBCC), Quiron Group, Madrid and Barcelona, Spain and Vall d'Hebron Institute of Oncology, Barcelona, Spain, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain
  18. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; The Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, Australia , Melbourne, Australia

Aims: In the phase 3 KEYNOTE-355 trial (NCT02819518), pembrolizumab+chemotherapy significantly improved OS and PFS versus placebo+chemotherapy in patients with previously untreated locally recurrent inoperable/metastatic TNBC with PD-L1 combined positive score (CPS) ≥10.1,2 There were no significant differences between treatment groups in the CPS ≥1 population, and significance was not tested in the ITT population due to the prespecified testing strategy. Here, we compare outcomes in subgroups of patients by additional CPS cut-offs to the primary results of KEYNOTE-355.

Methods: Eligible patients with measurable disease per RECIST v1.1, ECOG PS 0‒1, and ≥6-month disease-free interval were randomized 2:1 to pembrolizumab+chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine+carboplatin) or placebo+chemotherapy for up to 35 administrations of pembrolizumab/placebo or until progression/intolerable toxicity. Dual primary endpoints were OS and PFS (RECIST v1.1, BICR) in patients with PD-L1–positive tumors (CPS ≥10 and ≥1) and in the ITT population.

Results: 847 patients were randomized. Median time from randomization to data cutoff  (June 15, 2021) was 44 months. Baseline characteristics of the CPS 1‒9, 10‒19, and ≥20 subgroups were generally similar to those of the ITT population. In the primary analyses, HRs (95% CI) for OS were 0.73 (0.55‒0.95) in the CPS ≥10 subgroup, 0.86 (0.72‒1.04) in the CPS ≥1 subgroup, and 0.89 (0.76‒1.05) in the ITT population; HRs (95% CI) for PFS were 0.66 (0.50‒0.88), 0.75 (0.62‒0.91), and 0.82 (0.70‒0.98), respectively. HRs (95% CI) for the additional CPS subgroups were, for OS: CPS 1‒9, 1.09 (0.85‒1.40); CPS 10‒19, 0.71 (0.46‒1.09); and CPS ≥20, 0.72 (0.51‒1.01); and for PFS: CPS 1‒9, 0.85 (0.65‒1.11); CPS 10‒19, 0.70 (0.44‒1.09); and CPS ≥20, and 0.62 (0.44‒0.88).

Conclusions: These results provide support that CPS ≥10 is a reasonable cut-off to define the population of patients with metastatic TNBC expected to derive treatment benefit from pembrolizumab+chemotherapy.

  1. Cortes J, et al. Lancet. 2020;396:1817-1828.
  2. Cortes J, et al. N Engl J Med 2022;387:217-226.