Results of a large randomised trial showed no survival improvement in previously treated metastatic triple-negative breast cancer (TNBC) with single-agent pembrolizumab versus chemotherapy.
Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, presented findings from his team’s randomised trial KEYNOTE-119, which compared pembrolizumab monotherapy versus single-agent chemotherapy as second or third-line therapy for metastatic TNBC. Investigators randomised 622 patients to the two treatment arms. The primary analysis in patients with a PD-L1 combined positive score (CPS) ≥10 showed a median overall survival (OS) of 12.7 months with pembrolizumab and 11.6 months with investigator’s choice of chemotherapy. No significant advantage for pembrolizumab was seen in analyses of patients with CPS ≥1 and the overall population.
Pembrolizumab led to fewer grade 3/4 treatment-related adverse events (TRAEs). The most common grade 3/4 TRAEs all more often with chemotherapy, with serious AEs occurring in 20% of each group.
After a median follow-up of 31 months, analysis of the CPS ≥10 subgroup showed the pembrolizumab arm had a non-significant 22% reduction in the survival hazard. The CPS ≥1 analysis yielded median OS values of 10.7 months for the pembrolizumab arm and 10.2 months for the chemotherapy arm. Analysis of the overall population showed a median OS of 9.9 months with pembrolizumab and 10.8 months with chemotherapy. There was some evidence from a post hoc exploratory analysis that pembrolizumab activity might increase with higher CPS values.
“These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, especially those with PD-L1-enriched tumours, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer,” the researchers concluded.
The findings are consistent with the history of single-arm anti-PD-1/L1 therapy for breast cancer, said Eitan Amir, MD, and David W Cescon, MD, PhD, both of Princess Margaret Cancer Center in Toronto. In all types of breast cancer, checkpoint inhibitors have produced low response rates, but this has been consistent.
“Given the low response rates observed in the overall population with pretreated triple-negative breast cancer in previous studies of anti-PD-1 or anti-PD-L1 monotherapy, the primary results of KEYNOTE-119 are unsurprising,” they wrote. “Since KEYNOTE-119 was launched, clinical development has focused principally on combinations of chemotherapy and immunotherapy in the first-line setting.”
Drs Amir and Ceson cautioned that the results of the post hoc analysis are intriguing but must be treated with caution.
“The finding that this higher PD-L1 expression threshold might be a predictor of pembrolizumab monotherapy benefit adds to previously observed associations with single-drug immunotherapy benefit, including de novo metastatic disease, absence of previous chemotherapy, normal lactate dehydrogenase, lung or nodal involvement, and absence of liver metastases […] . It would be intriguing to see if similar results can be validated in triple-negative breast cancer,” Amir and Cescon added.
Source: MedPage Today
