13 Dec 2016
New interim data investigating anti-PD-1 pembrolizumab in combination with microtubule dynamics inhibitor eribulin in patients with metastatic triple-negative breast cancer (TNBC) was presented during the 2016 San Antonio Breast Cancer Symposium (SABCS).
These results were based on interim data from 39 evaluable patients who show an overall response rate (ORR) of 33.3% (n=13/39; 95% CI, 19.5-48.1), with one complete response and 12 partial responses.
ORR was similar between PD-L1-positive and -negative cohorts [PD-L1 positive=29.4% (n=5/17; 95% CI, 11.1-51.1).
Triple-negative breast cancer is an aggressive type of breast cancer where the cancer cells do not have oestrogen or progesterone receptors and do not have HER2, a growth-promoting protein.
Approximately 12% of breast cancer patients are diagnosed with triple-negative breast cancer.
Triple-negative breast cancer tends to grow and spread quickly.
Specifically, patients with triple-negative breast cancer are nearly two times more likely to have distant metastatic disease than those with most other types of breast cancer.
It is estimated that approximately five percent to 10 percent of women with breast cancer will have metastatic disease at the time of diagnosis.
Of these women, an estimated one in five is expected to survive five years.
The single-arm, multi-center phase 1b/2 study is investigating the combination of pembrolizumab (200 mg intravenously on Day 1) with eribulin mesylate (1.4 mg/m2 intravenously on Day 1 and Day 8) in 21-day cycles in 95 patients with metastatic TNBC who had previously been treated with up to two lines of chemotherapy.
The primary endpoint of the phase 1b portion of the study is to assess the safety and tolerability of the combination; for the phase 2 portion of the study, the primary endpoint is investigator-assessed ORR and secondary endpoints include progression-free survival, overall survival and duration of response as well as efficacy in a subset of patients with PD-L1-positive tumours.
At the time of data cutoff (July 12, 2016), 89 patients were enrolled, 39 of whom were evaluable.
The study is being conducted under an existing clinical trial collaboration agreement between Merck/MSD and Eisai.
There were 10 discontinuations due to treatment-emergent adverse events and no treatment-related deaths.
“Little progress has been made in metastatic triple-negative breast cancer, which is an aggressive and difficult-to-treat cancer. This initial evaluation of the combination of pembrolizumab and eribulin is encouraging and represents an important part of our multi-pronged effort to bring forward new potential approaches for patients with this type of cancer,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories.
“Patients with metastatic triple-negative breast cancer have a limited number of treatment options, making clinical study of new potential therapeutic approaches essential,” said Alton Kremer, M.D., Ph.D., chief clinical officer and chief medical officer, Oncology Business Group at Eisai. “With this ongoing study, we hope to learn more about the potential of pembrolizumab as part of a combination regimen with eribulin, with the long-term goal of addressing the unmet medical needs of patients with metastatic triple-negative breast cancer.”
“In addition to anti-mitotic effects, in preclinical and translational studies, eribulin induced tumour vascular remodelling, reduction of hypoxia and promotion of the less aggressive epithelial phenotype in advanced breast cancer tumour tissue. We look forward to further understanding how these effects of eribulin on tumour biology and microenvironment may impact the effect of pembrolizumab on the immune system’s T cells,” said Sara Tolaney, M.D., MPH, medical oncologist, Dana-Farber Cancer Institute, Boston, and the principal investigator of the study.
The most common treatment-emergent adverse events (incidence greater than or equal to 35%) for the combination regimen were fatigue (n=29; 74.4%), nausea (n=20; 51.3%), peripheral neuropathy (n=17; 43.6%), neutropenia (n=15; 38.5%), and alopecia (n=14; 35.9%), with grade 3 or higher treatment-emergent adverse events observed in 66.7% (n=26) of patients.
The two most common grade 3 or higher treatment-emergent adverse events observed were neutropenia (n=12; 30.8%) and fatigue (n=3; 7.7%).
The possible immune-mediated adverse events of clinical interest with pembrolizumab (grade 3/4) included rash (n=2; 5.1%), pneumonitis (n=1; 2.6%), hyperglycemia (n=1; 2.6%), renal failure (n=1; 2.6%) and rash generalized (n=1; 2.6%).
Events of clinical interest for eribulin (grade 3/4) included neutropenia (n=11, 28.2%), febrile neutropenia (n=1; 2.6%), and peripheral neuropathy (n=1; 2.6%).
Eribulin mesylate injection is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease.
Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Pembrolizumab is not indicated in any type of breast cancer.
This release discusses investigational uses for FDA-approved products.
This release is not intended to convey conclusions about efficacy or safety.
There is no guarantee that any investigational uses of such FDA-approved products will successfully complete clinical development or gain FDA approval.
Source: SABCS 2016