Cathy Eng, MD, FACP, FASCO
Cathy Eng, MD, FACP, FASCO, the David H. Johnson Endowed Chair in Surgical and Medical Oncology, Co-Director of Gastrointestinal Oncology, and Co-Leader of the Gastrointestinal Cancer Research Program at Vanderbilt-Ingram Cancer Center, Nashville, told The ASCO Post she finds the data from MOUNTAINEER “very promising and encouraging in previously treated patients.” The findings also demonstrate “the promise of participating in clinical trials, especially in rare patient populations,” she said.
MOUNTAINEER validates earlier findings from other trials, such as HERACLES,1 showing the benefit of trastuzumab in pretreated HER2-amplified cancers. In the current study, up to 40% of patients had received at least three lines of therapy, yet 38% of patients responded by blinded investigator review, and 65% had some reduction in tumor burden when trastuzumab was combined with tucatinib, she noted.
“The median progression-free survival of 8.2 months is quite impressive for such a heavily pretreated patient population, and the median overall survival was also quite impressive at 24.1 months,” Dr. Eng commented. “Overall, the regimen was tolerated well, with few grade 3 serious adverse events.”
Importance of HER2 Testing
“MOUNTAINEER further validates the importance of testing for HER2. Only 5% or less of all metastatic colorectal cancers will be HER2-positive, and efficacy is primarily seen in patients with IHC3+ [immunohistochemistry] or IHC2+/FISH [fluorescence in situ hybridization] amplified,” she noted. “Prior studies have also indicated that patients who are HER2-positive have less benefit from anti-EGFR [epidermal growth factor receptor] agents. Therefore, I would encourage providers to test for HER2 when considering anti-EGFR therapy.”
A phase III trial will evaluate tucatinib plus trastuzumab in combination with FOLFOX (fluorouracil, leucovorin, oxaliplatin). Also being investigated in HER2-positive patients is the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki, which has demonstrated efficacy in patients previously treated with trastuzumab.
DISCLOSURE: Dr. Eng reported no conflicts of interest.
REFERENCE
1. Sartore-Bianchi A, Trusolino L, Martino C, et al: Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 17:738-746, 2016.
