Results from the phase II MyPathway basket trial found that the HER2-targeted therapies pertuzumab and trastuzumab demonstrated durable activity in patients with a wide variety of tumors marked by HER2 amplification or overexpression, although responses were limited in those with KRAS mutations. These findings were presented during the 2021 ASCO Annual Meeting by Funda Meric-Bernstam, MD, and colleagues (Abstract 3004).
This trial truly demonstrated the value of the basket trial design in assessing efficacy across tumor types, as well as the impact of co-alterations.— Funda Meric-Bernstam, MD
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Pertuzumab and trastuzumab are antibody therapies that bind to HER2 and block its activity. HER2 is amplified or overexpressed in 2% to 3% of all solid tumors, but therapies against HER2 only are approved for breast, gastric, and gastroesophageal cancers.
MyPathway Trial
The study enrolled 258 patients across a variety of tumor types, excluding those for which the therapies already are approved. The most common cancer types enrolled were colorectal, biliary, and non–small cell lung cancers. Side effects recorded in the study were consistent with previous reports of these drugs.
Sixty patients (23.3%) had a confirmed objective response, indicating tumor shrinkage, including five complete responses. The disease control rate was 44.6%, and duration of response was 7.9 months. Notably, patients with KRAS mutations did not have a high response rate, with just one objective response reported among 26 patients.
"This trial truly demonstrated the value of the basket trial design in assessing efficacy across tumor types, as well as the impact of coalterations," said Dr. Meric-Bernstam, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "These agents were active in a wide variety of KRAS wild-type, HER2-amplified or -overexpressed tumor types, with notable activity in colorectal cancer and salivary tumors. However, there was limited activity in KRAS-mutant tumors, emphasizing that in precision oncology, we need to consider the full genomic profile in treatment selection."
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
