Phase II Basket Trial of Dual HER2-Targeted Therapy in Metastatic Breast Cancer
Patients with heavily pretreated HER2-mutated, hormone receptor–positive, HER2-nonamplified metastatic breast cancer seem to benefit from treatment with neratinib plus trastuzumab and fulvestrant, according to Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. The phase II SUMMIT trial results, which were presented during the virtual 2020 San Antonio Breast Cancer Symposium (SABCS; Abstract PD1-05), suggested this dual HER2-targeted therapy also had a manageable toxicity profile.
“HER2 mutations are oncogenic in hormone receptor–positive metastatic breast cancer and may confer resistance to prior endocrine therapy but retain sensitivity to neratinib,” the investigators commented. “Neratinib is an oral, irreversible, pan-HER tyrosine kinase inhibitor with clinical activity either as a single agent or in combination with fulvestrant in HER2-mutated, HER2-nonamplified metastatic breast cancer.”
A total of 46 patients were administered neratinib plus trastuzumab and fulvestrant. During the first two cycles, loperamide prophylaxis was mandatory.
The most commonly reported adverse event was diarrhea (any grade: 80%; grade 3: 33%). No patients discontinued treatment due to this toxicity, but the neratinib dose was reduced in 22% of the study population. The confirmed objective response rate was 40% in those who were eligible for the efficacy analysis, with 12 partial responses. A clinical benefit rate of 47% was reported. The median duration of response and progression-free survival was 8.4 and 8.3 months, respectively. Neratinib plus trastuzumab and fulvestrant also demonstrated clinical activity in patients who had previously received either fulvestrant or CDK4/6 inhibitor–based therapies.
“SUMMIT has recently been amended to evaluate neratinib plus trastuzumab and fulvestrant, trastuzumab plus fulvestrant, and fulvestrant (1:1:1 randomization) and continues to enroll patients,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit sabcs.org.
