In an updated analysis of a cohort in the phase IIa MyPathway study published in the Journal of Clinical Oncology, Christopher J. Sweeney, MBBS, and colleagues described outcomes with the combination of pertuzumab and trastuzumab in nonindicated HER2-altered advanced solid tumors.
As stated by the investigators, “The MyPathway multiple-basket study (ClinicalTrials.gov identifier NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab [plus] trastuzumab in a tissue-agnostic cohort of adult patients with HER2-amplified and/or HER2-overexpressed and/or HER2-mutated solid tumors.”
Christopher J. Sweeney, MBBS
Study Details
In the U.S.-based international study, a HER2-altered cohort of 346 patients with advanced solid tumors was enrolled between April 2014 and June 2019; a total of 263 patients had HER2 amplification and/or overexpression with/without HER2 mutations, and 83 had HER2 mutations alone. The most common cancers were colorectal cancer (27.5%), non–small cell lung cancer (17.3%), biliary tract cancer (14.7%), and gynecologic cancers (12.7%). The primary endpoint was objective response rate.
Key Findings
Among 263 patients with HER2 amplification and/or overexpression, an objective response was observed in 68 (25.9%, 95% confidence interval [CI] = 20.7%–31.6%); complete response was observed in 5 patients, including 2 each with urothelial and salivary gland cancers and 1 with colon cancer. Median duration of response was 7.4 months (95% CI = 5.9–9.2 months). The disease control rate was 45.2%. The objective response rate was higher among 203 patients with known wild-type KRAS vs 28 with known KRAS-mutant disease (28.1% vs 7.1%).
Among 142 patients with HER2 amplification, objective response rates were higher among patients with immunohistochemistry (IHC) of 3+ (32 of 78; 41.0%) and 2+ (7 of 32; 21.9%) compared those with 1+ (1 of 12; 8.3%) and no expression (0 of 20; 0%).
Among 83 patents with HER2 mutations alone, objective response was observed in 5 (6.0%, 95% CI = 2.0%–13.5%). Median duration of response was 7.4 months (95% CI = 1.4 months to not evaluable). The disease control rate was 32.5%.
The investigators concluded, “Pertuzumab [plus] trastuzumab showed activity in various HER2-amplified and/or -overexpressed tumors with wild-type KRAS, with the range of activity dependent on tumor type, but had limited activity in the context of KRAS mutations, HER2 mutations alone, or 0-1+ HER2 expression.”
Dr. Sweeney, of the South Australian Immunogenomics Cancer Institute, University of Adelaide, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann-La Roche/Genentech and the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
