Abstract PS12-01: Pembrolizumab versus chemotherapy for previously treated metastatic triple-negative breast cancer (KEYNOTE-119): Efficacy in patients with lung or liver metastases
Authors: Winer Eric , Lipatov Oleg , Im Seock-Ah , Goncalves Anthony , Lee Keun Seok , Schmid Peter , Testa Laura , Witzel Isabell , Ohtani Shoichiro , Turner NIcholas , Zambelli Stefania , Harbeck Nadia , Andre Fabrice , Dent Rebecca , Lin Jianxin , Karantza Vassiliki , Mejia Jaime , Cortes Javier 
Published: February 2021

Abstract
Background: KEYNOTE-119 (NCT02555657) is a randomized, open-label phase 3 study of pembrolizumab (pembro) monotherapy vs single-agent chemotherapy (chemo) in patients with previously treated metastatic triple-negative breast cancer (mTNBC). The results showed directionally favorable improvement in overall survival (OS) with pembro compared to chemo in patients with PD-L1−positive tumors, although statistical superiority was not demonstrated. The pembro treatment effect increased with PD-L1 enrichment, as measured by the combined positive score (CPS). Since treatment outcomes may vary by location of metastasis, we performed a retrospective, exploratory analysis to evaluate the efficacy of pembro vs chemo among patients with lung or liver metastasis at baseline enrolled in KEYNOTE-119.
Methods: Patients with centrally confirmed TNBC, 1-2 prior systemic treatments for metastatic disease, documented progression on most recent therapy and prior treatment with an anthracycline and/or taxane were randomized 1:1 to pembro 200 mg Q3W or single-agent chemo per investigator’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine (60% enrollment cap for each). Patients were stratified by PD-L1 status (CPS &lt;1 vs ≥1) and history of prior neoadjuvant/adjuvant treatment vs de novo metastatic disease at initial diagnosis. Primary study end points were OS in patients with PD-L1 CPS ≥10, patients with CPS ≥1, and all patients.
Results: Overall, 622 patients were randomized in KEYNOTE-119 (pembro, n=312; chemo, n=310); median follow-up was 31 months at the April 11, 2019 data cutoff date. At baseline, 403 (65%) patients had lung metastasis and 173 (28%) had liver metastasis. Pembro did not improve OS vs chemo in patients with lung or liver metastases in the ITT population, although the HRs decreased as tumor PD-L1 expression increased, with the greatest benefit observed in patients with PD-L1 CPS ≥20 tumors (Table). Similar trends were observed for progression-free survival, objective response rate, and duration of response. In both treatment groups, presence of liver metastases at baseline was associated with shorter OS as compared to absence of liver metastases at baseline; this trend was not observed for lung metastases. Results should be interpreted with caution due to modest patient sample size in some subgroups.
Conclusion: Among patients with previously treated mTNBC who had lung or liver metastases for whom prognosis is typically poor, pembro monotherapy showed a benefit vs single-agent chemo in patients with increasing PD-L1 tumor enrichment. These findings are consistent with the results from the global study population.
Table. Analysis of Overall SurvivalITTCPS ≥1CPS ≥10CPS ≥20NMedian, mo (95% CI)HR (95% CI)NMedian, mo (95% CI)HR (95% CI)NMedian, mo (95% CI)HR (95% CI)NMedian, mo (95% CI)HR (95% CI)Patients With Lung MetastasesPembro2009.8 (7.4-11.7)0.99 (0.80-1.23)12710.6 (8.1-12.5)0.85 (0.65-1.10)5612.8 (9.3-17.2)0.80 (0.53-1.18)3117.0 (11.7-27.1)0.55 (0.32-0.95)Chemo20311.4 (8.7-13.1)13110.4 (7.2-12.7)6311.9 (7.3-14.9)3413.0 (7.2-15.8)Patients Without Lung MetastasesPembro11210.3 (8.3-13.6)0.92 (0.69-1.23)7610.8 (8.9-15.7)0.89 (0.63-1.26)4012.1 (8.6-16.4)0.79 (0.47-1.31)2612.8 (7.8-23.0)0.63 (0.32-1.24)Chemo10710.2 (7.2-12.7)719.9 (7.0-13.5)3511.3 (7.0-15.7)1810.5 (5.2-15.7)Patients With Liver MetastasesPembro876.5 (4.7-9.3)1.04 (0.76-1.43)577.7 (4.2-9.9)1.02 (0.69-1.51)2410.3 (6.2-16.4)0.78 (0.44-1.39)1310.7 (6.2-19.0)0.69 (0.31-1.53)Chemo866.5 (5.4-8.4)546.5 (5.4-7.8)317.2 (5.2-11.6)207.5 (2.9-14.7)Patients Without Liver MetastasesPembro22510.9 (9.2-12.6)0.95 (0.78-1.17)14612.4 (10.5-14.2)0.82 (0.64-1.05)7213.0 (10.1-17.2)0.80 (0.55-1.16)4416.0 (11.4-27.1)0.57 (0.33-0.95)Chemo22412.6 (10.6-13.9)14812.6 (9.8-13.6)6712.7 (9.8-15.8)3214.3 (8.3-16.8)
Citation Format: Eric Winer, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Keun Seok Lee, Peter Schmid, Laura Testa, Isabell Witzel, Shoichiro Ohtani, NIcholas Turner, Stefania Zambelli, Nadia Harbeck, Fabrice Andre, Rebecca Dent, Jianxin Lin, Vassiliki Karantza, Jaime Mejia, Javier Cortes. Pembrolizumab versus chemotherapy for previously treated metastatic triple-negative breast cancer (KEYNOTE-119): Efficacy in patients with lung or liver metastases [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-01.