Researchers have found that 2%–3% of all solid tumors overexpress or amplify HER2 protein that may be a target for drugs such as pertuzumab and trastuzumab, particularly in KRAS-variant disease. They presented their findings during the 2021 American Society of Clinical Oncology annual meeting.
The results were from a phase II basket study of 258 adult patients with HER2-amplified or overexpressed colorectal, biliary, non-small cell lung, uterine, urothelial, salivary, ovarian, pancreatic, and other cancers. The patients received pertuzumab (840 mg loading dose followed by 420 mg every three weeks) and trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every three weeks) until they experienced disease progression or unacceptable toxicity.
Five patients had complete responses and 55 had partial responses. The median duration of response was 7.9 months, median progression-free survival (PFS) was 2.8 months, and median overall survival (OS) was 10.9 months. Patients with salivary (63.6%), pancreatic (33.3%), or colorectal cancer (30.9%) had the highest responses, and those with uterine (6.3%) or ovarian cancer (10.0%) had the lowest.
Overall response rates were 25.6% in patients with wild-type KRAS and 3.8% in patients with KRAS-variant tumors. Median PFS was 3.9 months and 1.4 months and median OS was 12.6 months and 5.7 months in the wild-type KRAS and KRAS-variant groups, respectively.
The findings may pave the way for expanding HER2-targeted therapies beyond their currently approved indications for breast, gastric, and gastroesophageal cancers. “Our data suggests that HER2-targeted therapy may have utility in a variety of HER2-positive, KRAS wild-type tumors,” the researchers said. “It also demonstrates the value of biomarker-driven basket trials for assessing efficacy across tumor types while enhancing the ability to determine the impact of coalterations on antitumor efficacy.”