SAN ANTONIO — Pembrolizumab plus trastuzumab appeared well-tolerated and showed clinical benefit among women with advanced HER-2-positive breast cancer with PD-L1-positive tumors that were resistant to trastuzumab, according to results from the PANACEA study presented at the San Antonio Breast Cancer Symposium.
“HER-2-posiitve breast cancers have been observed to contain high-levels of T-cell infiltration. We wanted to investigate if immunotherapy approaches can work in patients with advanced HER-2-positive breast cancer that is resistant to trastuzumab [Herceptin, Genentech],” Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, said during a press briefing.
The single-arm phase 1b/phase 2 trial included 58 patients (median age, 50.5 years) with advanced breast cancer who progressed on prior trastuzumab-based therapies. Researchers assessed tumors centrally for HER-2 positivity and PD-L1 status, and for quantity of tumor-infiltrating lymphocytes (TILs).
In the phase 1b portion of the trial, patients received 2 mg/kg pembrolizumab (Keytruda, Merck) plus 10 mg/kg IV trastuzumab every 3 weeks. In the phase 2 portion, patients received 200 mg IV pembrolizumab with trastuzumab every 3 weeks.
Researchers did not observe any dose-limiting toxicities in the phase 1b phase.
Objective response by RECIST served as the study’s primary outcome; secondary outcomes included PFS, OS, disease-control rate, duration of response and duration of disease control.
Researchers reported an ORR of 15.2% and a disease control rate of 24% in the PD-L1-positive cohort. In a subgroup of these patients with 5% of more TILs present in the metastatic lesion, ORR increased to 39% and disease control rate to 47%.
“Stromal TIL levels in the metastatic lesion were associated with response, and a TIL level greater than 5% could enrich this cohort for a high response rate,” Loi said.
However, no objective responses were observed in the PD-L1-negative cohort.
Disease control appeared durable among those patients in the PD-L1-positive cohort who experienced an objective response or stable disease, with a median duration of 11.1 months.
“At the time I am reporting these data, five patients continue with no disease progression and at least two patients have completed 2 years on pembrolizumab,” Loi said.
Adverse outcomes included grade 1/grade 2 fatigue (21%), grade 1/grade 2 hyper- and hypothyroidism (6.9%) and grade 3/ grade 4 pneumonitis (3.4%).
“Future directions for immuno-oncology in HER-2-positive metastatic disease should focus on combinations with an effective anti-HER-2 therapy, particularly in low TIL patients,” Loi said. – by Jennifer Southall
Loi S, et al. Abstract GS2-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: The study was sponsored and managed by the International Breast Cancer Study Group in collaboration with the Breast International Group, and funded by a Merck subsidiary. Loi reports no relevant financial disclosures. Please see the abstract for all other others’ relevant financial disclosures.