Keytruda May Not Improve Overall Survival Versus Chemotherapy in Metastatic Triple-Negative Breast Cancer


Although Keytruda did not improve overall survival when compared with chemotherapy, patients with a higher PD-L1 expression may derive a greater benefit with Keytruda, as shown with a longer median overall survival.

Keytruda (pembrolizumab) did not significantly improve overall survival compared with chemotherapy in patients with previously treated metastatic triple-negative breast cancer, according to a study published in The Lancet Oncology.

The data also suggested that patients with a higher PD-L1 expression who were treated with Keytruda had longer median overall survival.

“Although results from exploratory analyses must be considered hypothesis-generating, it appears that the highest benefit with (Keytruda) was observed in an unplanned subset of participants with strongly positive PD-L1-expressing tumors (combined positive score ≥ 20), comprising approximately 18% of the overall study population,” the study authors wrote.

In particular, Keytruda is an anti-PD-1 antibody that blocks the interaction between PD-L1 and PD-L2 receptors, which then allows the activation of an antitumor response. PD-L1 is often expressed in half of all breast cancers and up to 30% of patients with triple-negative breast cancer. A combined positive score which uses the number of PD-L1 staining cells and divides that by the total number of viable tumor cells.

In this phase 3 trial, researchers analyzed data from 622 patients with metastatic triple-negative breast cancer who previously received one or two systemic treatments for their disease. These patients have also had disease progression on their most recent therapy and were previously treated with a taxane or anthracycline.

Patients were assigned 200 mg of Keytruda once every three weeks for 35 cycles (312 patients; median age, 50 years; 100% women) or single-drug chemotherapy (310 patients; median age, 53 years; 99% women), which included Halaven (eribulin), capecitabine, vinorelbine or gemcitabine.

Several factors were assessed throughout the trial including overall survival, defined as the time from randomization in the trial to all-cause death. This was analyzed in patients with a PD-L1 combined positive score of 10 or more, a combined positive score of one or more and also in all patients. Follow-up was conducted for a median of 31.4 months in the Keytruda group and 31.5 months in the chemotherapy group.

In patients with a combined positive score of 10 or more, the median overall survival was 12.7 months for those assigned Keytruda compared with 11.6 months in those assigned chemotherapy. For patients with a combined positive score of one or more, the Keytruda group had a median overall survival of 10.7 months versus 10.2 months in the chemotherapy group. When researchers assessed the overall trial population, median overall survival was 9.9 months for patients assigned Keytruda compared with 10.8 months for those assigned chemotherapy.

The most common serious or life-threatening side effects in patients assigned Keytruda or chemotherapy included decreased white blood cells (< 1% versus 5%, respectively), anemia (1% versus 3%, respectively), neutropenia (13% versus 20%, respectively) and decreased neutrophil count (< 1% versus 10%, respectively).

Less than 1% of patients had side effects related to the treatment that led to death, which occurred in less than 1% of patients assigned Keytruda and 1% of those assigned chemotherapy. The death that occurred in the Keytruda group was linked with circulatory collapse, whereas the two deaths in the chemotherapy group were linked to sepsis/pancytopenia (low counts of white blood cells, red blood cells and platelets) and hemothorax (collection of blood between the chest wall and lungs).

“The safety profile of (Keytruda) in metastatic triple-negative breast cancer in this study was generally consistent with the established safety profile of (Keytruda) monotherapy,” the study authors wrote. “No new immune-mediated (side effects) causally related to (Keytruda) were identified.”

The study authors also mentioned that these findings may aid in future research efforts. They wrote, “Taken together, these findings might inform future research of (Keytruda) monotherapy for selected subpopulations of patients, specifically those with PD-L1 enriched tumors, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer.”

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