KEYNOTE-119: Pembrolizumab no additional OS benefit in second-, third-line TNBC
medwireNews: Previously treated patients with triple-negative breast cancer (TNBC) do not have better overall survival (OS) with pembrolizumab than chemotherapy, although those with high PD-L1 expression may derive some benefit, suggest results of KEYNOTE-119.
“These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, specifically those with PD-L1 enriched tumours, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer,” write Eric Winer (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and team in The Lancet Oncology.
The phase 3 trial investigators randomly assigned 622 patients from 31 countries who had received one or two prior treatments for metastatic TNBC to receive pembrolizumab 200 mg every 3 weeks for 35 cycles or an investigator’s choice of single-agent chemotherapy, either capecitabine, eribulin, gemcitabine, or vinorelbine.
Patients in the intention-to-treat (ITT) population had similar median overall survival (OS) with pembrolizumab and chemotherapy, at 9.9 versus 10.8 months, after a median follow-up of 31.4 and 31.5 months, respectively.
The findings were similar in the 65% of patients with a combined positive score (CPS) for PD-L1 expression of at least 1 and the 31% with a CPS of at least 10; the median OS durations with pembrolizumab and chemotherapy were 10.7 versus 10.2 months and 12.7 versus 11.6 months, respectively.
Secondary endpoints, such as progression-free survival, objective response rate, and disease control rate, also did not significantly differ between the two treatment groups in the ITT population.
However, post-hoc exploratory analysis suggested that the 18% of patients with a CPS of 20 or more had a significantly longer median OS with pembrolizumab than chemotherapy, at 14.9 versus 12.5 months, and a hazard ratio for death of 0.58.
Winer et al also highlight that “the pembrolizumab treatment effect increased as tumour PD-L1 expression increased,” and postulate that “prospective assessment of higher PD-L1 cutoffs might be of value.”
Reporting on the safety profile, the investigators say that “pembrolizumab had less high-grade toxicity compared with chemotherapy,” with 14% versus 36% of patients in the respective treatment groups having a grade 3–4 treatment-related adverse event (AE). And a fifth of patients in each treatment arm had a serious adverse event, most commonly pleural effusion (2 vs 1%), pneumonia (2 vs 2%), and febrile neutropenia (<1 vs 2%).
Nine deaths in each treatment arm were attributed to AEs.
In an accompanying comment, Eitan Amir and David Cescon, both from Princess Margaret Cancer Centre Toronto in Ontario, Canada, say: “Although disappointing to observe that pembrolizumab did not improve overall survival compared with chemotherapy, an important finding was the possible association between improved activity of pembrolizumab and increasing CPS.”
They emphasize, however, that the analysis of PD-L1-high tumors “was exploratory and hypothesis-generating, with only about one in six participants having a PD-L1 CPS of 20 or more.”
And the commentators conclude: “Although restricting the overall effects of these results, this observation is nevertheless of interest and warrants exploration.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group