MyPathway human epidermal growth factor receptor 2 basket study: Pertuzumab + trastuzumab treatment of a tissue-agnostic cohort of patients with human epidermal growth factor receptor 2-altered advanced solid tumors.
Creators: name: Sweeney, Christopher J
name: Hainsworth, John D
name: Bose, Ron
name: Burris, Howard A
name: Kurzrock, Razelle
name: Swanton, Charles
name: Friedman, Claire F
name: Spigel, David R
name: Szado, Tania
name: Schulze, Katja
name: Price, Richard
name: Malato, Julia
name: Lo, Amy A
name: Levy, Jonathan
name: Wang, Yong
name: Yu, Wei
name: Meric-Bernstam, Funda
Publisher: name: The Francis Crick Institute
Year: 2024
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Signalling & Oncogenes
subject: Signalling &amp; Oncogenes
classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Genome Integrity & Repair
subject: Genome Integrity &amp; Repair
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology

description: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The MyPathway multiple-basket study (ClinicalTrials.gov identifier: NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab + 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 = 263), or HER2 mutations alone (n = 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 = 2], salivary gland [n = 2], and colon [n = 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) 3+ (41.0%; 32/78) or 2+ (21.9%; 7/32), versus 1+ (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 + 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.