Results from the Randomized KEYNOTE-355 Study of Pembrolizumab Plus Chemotherapy for Asian Patients with Advanced TNBC

Overview

Journal NPJ Breast Cancer

Date 2024 Sep 12

PMID 39266535

Authors

Seock-Ah Im

Javier Cortes

David W Cescon

Mastura Md Yusof

Hiroji Iwata

Norikazu Masuda

Toshimi Takano

Chiun-Sheng Huang

Chi-Feng Chung

Koichiro Tsugawa

Yeon Hee Park

Koji Matsumoto

Kenichi Inoue

Ava Kwong

Sherene Loi

Wei Fu

Wilbur Pan

Vassiliki Karantza

Hope S Rugo

Peter Schmid

Affiliations

Soon will be listed here.

Abstract

In the phase 3 KEYNOTE-355 study (NCT02819518), pembrolizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy among patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10 tumors. We analyzed outcomes for the subgroup of patients enrolled in Asia in KEYNOTE-355. Patients received pembrolizumab 200 mg or placebo (2:1 randomization) every 3 weeks for 35 cycles plus investigator's choice chemotherapy. Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 and OS. Among patients enrolled in Hong Kong, Japan, Korea, Malaysia and Taiwan (pembrolizumab plus chemotherapy, n = 113; placebo plus chemotherapy, n = 47), 117 (73.1%) had PD-L1 CPS ≥ 1 and 56 (35.0%) had PD-L1 CPS ≥ 10. Median time from randomization to data cutoff (June 15, 2021) was 43.8 (range, 36.8‒53.2) months (intent-to-treat [ITT] population). Hazard ratios (HRs [95% CI]) for PFS in the CPS ≥ 10, CPS ≥ 1, and ITT populations were 0.48 (0.24‒0.98), 0.58 (0.37‒0.91), and 0.66 (0.44‒0.99), respectively. Corresponding HRs (95% CI) for OS were 0.54 (0.28‒1.04), 0.62 (0.40‒0.97), and 0.57 (0.39‒0.84). Grade 3/4 treatment-related adverse events (AEs) occurred in 77.9% versus 78.7% of patients with pembrolizumab plus chemotherapy versus placebo plus chemotherapy. No grade 5 AEs occurred. Clinically meaningful improvement in PFS and OS with manageable toxicity were observed with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in patients enrolled in Asia with previously untreated, inoperable or metastatic TNBC.Trial registration: ClinicalTrials.gov, NCT02819518.

References

Gatalica Z, Snyder C, Maney T, Ghazalpour A, Holterman D, Xiao N . Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomarkers Prev. 2014; 23(12):2965-70. DOI: 10.1158/1055-9965.EPI-14-0654. View

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D . Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014; 25(8):1544-50. DOI: 10.1093/annonc/mdu112. View

Nanda R, Chow L, Dees E, Berger R, Gupta S, Geva R . Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016; 34(21):2460-7. PMC: 6816000. DOI: 10.1200/JCO.2015.64.8931. View

Nagahashi M, Ling Y, Hayashida T, Kitagawa Y, Futamura M, Yoshida K . Actionable gene alterations in an Asian population with triple-negative breast cancer. JCO Precis Oncol. 2020; 2. PMC: 7288901. DOI: 10.1200/po.17.00211. View

Wang C, Kar S, Lai X, Cai W, Arfuso F, Sethi G . Triple negative breast cancer in Asia: An insider's view. Cancer Treat Rev. 2017; 62:29-38. DOI: 10.1016/j.ctrv.2017.10.014. View

Winer E, Lipatov O, Im S, Goncalves A, Munoz-Couselo E, Lee K . Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(4):499-511. DOI: 10.1016/S1470-2045(20)30754-3. View

Kulkarni A, Kelkar D, Parikh N, Shashidhara L, Koppiker C, Kulkarni M . Meta-Analysis of Prevalence of Triple-Negative Breast Cancer and Its Clinical Features at Incidence in Indian Patients With Breast Cancer. JCO Glob Oncol. 2020; 6:1052-1062. PMC: 7392736. DOI: 10.1200/GO.20.00054. View

Hammond M, Hayes D, Wolff A, Mangu P, Temin S . American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 2010; 6(4):195-7. PMC: 2900870. DOI: 10.1200/JOP.777003. View

10.

Boyle P . Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012; 23 Suppl 6:vi7-12. DOI: 10.1093/annonc/mds187. View

11.

Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J . Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020; 382(9):810-821. DOI: 10.1056/NEJMoa1910549. View

12.

Adams S, Loi S, Toppmeyer D, Cescon D, De Laurentiis M, Nanda R . Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2018; 30(3):405-411. DOI: 10.1093/annonc/mdy518. View

13.

Kulangara K, Zhang N, Corigliano E, Guerrero L, Waldroup S, Jaiswal D . Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer. Arch Pathol Lab Med. 2018; 143(3):330-337. DOI: 10.5858/arpa.2018-0043-OA. View

14.

Adams S, Gray R, Demaria S, Goldstein L, Perez E, Shulman L . Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014; 32(27):2959-66. PMC: 4162494. DOI: 10.1200/JCO.2013.55.0491. View

15.

Iwata H, Inoue K, Kaneko K, Ito Y, Tsugawa K, Hasegawa A . Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130). Jpn J Clin Oncol. 2019; 49(12):1083-1091. PMC: 6935297. DOI: 10.1093/jjco/hyz135. View

16.

Han H, Reis I, Zhao W, Kuroi K, Toi M, Suzuki E . Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer. 2011; 47(17):2537-45. DOI: 10.1016/j.ejca.2011.06.027. View

17.

Cortes J, Cescon D, Rugo H, Nowecki Z, Im S, Yusof M . Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020; 396(10265):1817-1828. DOI: 10.1016/S0140-6736(20)32531-9. View

18.

Lu Y, Yeo W, Yap Y, Park Y, Tamura K, Li H . An Overview of the Treatment Efficacy and Side Effect Profile of Pharmacological Therapies in Asian Patients with Breast Cancer. Target Oncol. 2021; 16(6):701-741. PMC: 8613101. DOI: 10.1007/s11523-021-00838-x. View

19.

Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S . Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022; 386(6):556-567. DOI: 10.1056/NEJMoa2112651. View

20.

Cortes J, Rugo H, Cescon D, Im S, Yusof M, Gallardo C . Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022; 387(3):217-226. DOI: 10.1056/NEJMoa2202809. View