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
Year: 2023
Type: article
Abstract: 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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.22.02636
Institutions: The University of Adelaide, Sarah Cannon, Tennessee Oncology, Washington University in St. Louis, Medical College of Wisconsin Cancer Center, The Francis Crick Institute, University College London, Memorial Sloan Kettering Cancer Center, Cornell University, Weill Cornell Medicine, Genentech, The University of Texas MD Anderson Cancer Center
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, American Society of Clinical Oncology, Celgene, F. Hoffmann-La Roche, Karyopharm Therapeutics, Regeneron Pharmaceuticals, Taiho Pharmaceutical, Francis Crick Institute, Jazz Pharmaceuticals, Cholangiocarcinoma Foundation, Aeglea BioTherapeutics, Celldex Therapeutics, Novocure, Clovis Oncology, Tizona Therapeutics, Agios Pharmaceuticals, Jounce Therapeutics, BeiGene, Incyte, Calithera Biosciences, Tarveda Therapeutics, Apollomics, Puma Biotechnology, Moderna, MacroGenics, G1 Therapeutics, Seagen, Eisai, European Organisation for Research and Treatment of Cancer, Astellas Pharma, European Society for Medical Oncology, Menarini Group, Ipsen, National Institutes of Health, Genentech, University of Texas MD Anderson Cancer Center, National Cancer Institute, National Center for Advancing Translational Sciences, Daiichi Sankyo Europe
OpenAlex ID: W4387329018