Sara M. Tolaney, MD, MPH
The combination of eribulin (Halaven) and pembrolizumab (Keytruda) demonstrated promising objective response rates (ORR), including a complete response (CR), for patients with metastatic triple-negative breast cancer (TNBC), according to findings from a phase Ib/II study presented at the 2017 Miami Breast Cancer Conference.
In 39 evaluable patients at an interim analysis of the study, the ORR with the combination was 33.3% (95% CI, 19.5-48.1). The CR rate was 2.6% and 28.2% of patients had stable disease (SD) for ≥8 weeks, of which 7.7% was for ≥24 weeks. The clinical benefit rate (CBR; ORR plus SD for ≥24 weeks) was 41%.
"The combination of eribulin plus pembrolizumab demonstrated activity in patients with metastatic TNBC. Objective responses, including a complete response, were observed during this interim analysis," Sara M. Tolaney, MD, MPH, from the Dana-Farber Cancer Institute, and colleagues wrote in their poster. "In this study, PD-L1 positivity did not seem to predict response to treatment."
In the study, 89 total patients with metastatic TNBC received eribulin at 1.4 mg/m2
on days 1 and 8 plus pembrolizumab at a flat dose of 200 mg every 3 weeks. The median age of patients was 53 years (range, 32-80). The ECOG performance status was 0 (56.4%) and 1 (43.6%). In the metastatic setting, 43.6% of patients had no prior chemotherapy and 56.4% had received 1 to 2 prior lines of chemotherapy. Nearly half of patients in the study were PD-L1–positive (43.6%).
At the interim analysis, the median treatment duration was 3.9 months with eribulin and 3.7 months for pembrolizumab, which was equivalent to 6 cycles of each medication. The median duration of response was not yet reached, with most of the responders still benefiting. The CR was ongoing at 36 weeks, and all responses lasted greater than 16 weeks.
The ORR with the combination for untreated patients with metastatic TNBC (n = 17) was 41.2% (95% CI, 19.3-62.8). The SD for ≥8 weeks rate was 17.6% and the CBR was 47.1%. In a cohort of patients pretreated with 1 to 2 therapies (n = 22), the ORR was 27.3% (95% CI, 11.3-46.4), which included the 1 CR. The SD for ≥8 weeks rate was 36.4% and the CBR was 36.4%.
In patients with PD-L1–positive TNBC (n = 17), the ORR was 29.4% (95% CI, 11.1-51.1) and in those with PD-L1–negative disease (n = 18) the ORR was 33.3% (95% CI, 14.1-54.6). The 1 CR in the study was seen in a group of 4 patients with unavailable PD-L1 status.
Overall, 66.7% of patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). The most common grade 3/4 TEAEs were neutropenia (30.8%) and fatigue (7.7%). The most common TEAEs of all grades were fatigue (74.4%), nausea (51.3%), peripheral neuropathy (43.6%), neutropenia (43.6%), and alopecia (35.9%).
Possible immune-related TEAEs were experienced by 66.7% of patients, of which 12.8% were grade 3/4 events. The most common immune-related TEAEs included hypothyroidism (30.8%), rash (15.4%), hyperglycemia (12.8%), hyperthyroidism (10.3%) and pneumonitis (10.3%).
Across all 89 patients enrolled, 11.2% had a TEAE leading to study withdrawal. There were 3 fatal AEs in the trial, which were unrelated to treatment (respiratory failure, pleural effusion, and multiple organ dysfunction syndrome).
"AEs observed with the combination were comparable to those observed historically with either treatment as monotherapy," the authors wrote in the poster.
The data cutoff for the analysis was July 12, 2016. Longer follow-up from the trial for the full 89 patients are anticipated later this year. Additionally, a second phase II study will begin enrolling soon to assess pembrolizumab with or without eribulin for patients with HR-positive breast cancer (NCT03051659).<<< View more from the 2017 Miami Breast Cancer Conference