Updated results of the phase Ib/II ENHANCE1/KEYNOTE-150 study presented at the 2017 San Antonio Breast Cancer Symposium found that the combination of pembrolizumab (Keytruda) and eribulin (Halaven) was associated with a 26.4% objective response rate for patients with metastatic triple-negative breast cancer.
Sara Tolaney, MD, MPH
Updated results of the phase Ib/II ENHANCE1/KEYNOTE-150 study presented at the 2017 San Antonio Breast Cancer Symposium found that the combination of pembrolizumab (Keytruda) and eribulin (Halaven) was associated with a 26.4% objective response rate (ORR) for patients with metastatic triple-negative breast cancer (TNBC).
In the open-label study, the ORR with the combination for untreated patients with metastatic TNBC (n = 65) was 29.2% (95% CI, 18.6%-41.8%). In a cohort of patients pretreated with 1 to 2 therapies (n = 41), the ORR was 22.0% (95% CI, 10.6%-37.6%). Across all treatment arms, there were 3 complete responses to the combination (2.8%).
"The results observed, namely the response rates and tolerability achieved with the eribulin and pembrolizumab combination regimen, broaden our knowledge base as to the possible effect of these two agents when used together in patients with metastatic TNBC," said lead investigator Sara M. Tolaney, MD, MPH, from the Dana-Farber Cancer Institute, said in a statement. "The potential of the combination of eribulin plus pembrolizumab for this aggressive form of breast cancer is exciting for both patients and physicians alike."
The study enrolled 107 patients with metastatic TNBC who previously received 0 to 2 prior therapies. Eribulin was administered at 1.4 mg/m2on days 1 and 8 and pembrolizumab was given at a flat dose of 200 mg every 3 weeks. Overall, 106 patients were evaluable for efficacy. The media age of patients was 55.0 years (range, 32-88). The ECOG performance status was 0 (65.4%) and 1 (34.6%). Half of patients in the study were PD-L1-positive (45.8%). The median duration of treatment with eribulin was 19.0 weeks (range, 3.0-70.0) and 18.1 weeks with pembrolizumab (range, 3.0-72.0). Patients received a median of 6 cycles.
When including those with stable disease (SD) for ≥24 weeks, the clinical benefit rate (CBR; ORR plus SD) across all treatment settings was 36.8%. The median duration of response (DOR) was 8.3 months, and 14.3% of patients experienced a response for >12 months. In the frontline setting, the CBR was 40% and the median DOR was 8.3 months. In the second or third-line, the CBR was 31.7% and the median DOR had not yet been reached.
The median progression-free survival (PFS) across the full study was 4.2 months (95% CI, 4.1-5.6). In the frontline and second/third-line setting, the median PFS was 4.9 and 4.1 months, respectively. The median overall survival (OS) across all groups was 17.7 months (95% CI, 13.7 - not estimable). In the frontline and second/third-line setting, the median OS was 17.7 and 18.3 months, respectively.
Clinical activity was observed regardless of PD-L1 expression. In those who tested positive for the marker (n = 49), the ORR with the combination was 30.6%. In those who tested negative (n = 49), the ORR was 22.4%. Of the complete responses, 2 were in the positive subgroup and 1 was in the negative group.
Across all evaluable patients, grade 3 treatment-emergent adverse events (TEAE) were experienced by 47.7% and grade 4 TEAEs were experienced by 18.7% of patients. TEAEs led to dose reductions for 32% of patients and to study withdrawal for 22.4% of patients. Two of these events were in the phase Ib portion of the study and the remaining 22 were in phase II. There were 7 fatal AEs in the trial, which were each deemed to be unrelated to the combination.
The most common grade 3/4 TEAEs were neutropenia (30.8%), peripheral neuropathy (9.3%), and anemia, fatigue, and hypokalemia (5.6% each). The most common TEAEs of all grades were fatigue (73.8%), peripheral neuropathy (62.6%), nausea (61.7%), alopecia (42.1%), and constipation (39.3%).
"Most of the major advances in breast cancer treatment to date have been for patients whose cancers express the receptors currently identified as targets for treatment; limited options exist for patients with metastatic triple-negative breast cancer," Alton Kremer, MD, PhD, chief clinical officer and chief medical officer, Oncology Business Group at Eisai, the company developing eribulin, said in a statement.
"These updated results give us confidence to continue to study eribulin in the treatment of metastatic breast cancer in combination with new agents, like checkpoint inhibitors," he added. "We are very encouraged by the activity seen when adding pembrolizumab to eribulin, and we are eager to further assess these data and their meaning for patients with metastatic TNBC."
Tolaney SM, Kalinsky K, Kaklamani V, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract PD6-13.