MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab 1 Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2–Altered Advanced Solid Tumors

Christopher J. Sweeney, John D. Hainsworth, Ron Bose, Howard A. Burris, Razelle Kurzrock, Charles Swanton, Claire F. Friedman, David R. Spigel, Tania Szado, Katja Schulze, Richard Price, Julia Malato, Amy A. Lo, Jonathan Levy, Yong Wang, Wei Yu, Funda Meric-Bernstam

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5 Scopus citations

Abstract

The MyPathway multiple-basket study (ClinicalTrials.gov identifier: NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab 1 trastuzumab in a tissue-agnostic cohort of adult patients with human epidermal growth factor receptor 2 (HER2)–amplified and/or –overexpressed and/or –mutated solid tumors. The primary end point was objective response rate (ORR); secondary end points included survival and safety. At data cutoff (March 2022), 346 patients with HER2 amplification and/or overexpression with/without HER2 mutations (n 5 263), or HER2 mutations alone (n 5 83) had been treated. Patients with HER2 amplification and/or overexpression had an ORR of 25.9% (68/263, 95% CI, 20.7 to 31.6), including five complete responses (urothelial [n 5 2], salivary gland [n 5 2], and colon [n 5 1] cancers). Activity was higher in those with wild-type (ORR, 28.1%) versus mutated KRAS (ORR, 7.1%). Among patients with HER2 amplification, ORR was numerically higher in patients with immunohistochemistry (IHC) 31 (41.0%; 32/78) or 21 (21.9%; 7/32), versus 11 (8.3%; 1/12) or no expression (0%; 0/20). In patients with HER2 mutations alone, ORR was 6.0% (5/83, 95% CI, 2.0 to 13.5). Pertuzumab 1 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 0-11 HER2 expression.

Original languageEnglish
Pages (from-to)258-265
Number of pages8
JournalJournal of Clinical Oncology
Volume42
Issue number3
DOIs
StatePublished - Jan 20 2024

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