Sweeney, Christopher J;
Hainsworth, John D;
Bose, Ron;
Burris, Howard A;
Kurzrock, Razelle;
Swanton, Charles;
Friedman, Claire F;
... Meric-Bernstam, Funda; + view all
(2024)
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.
Journal of Clinical Oncology
, 42
(3)
pp. 258-265.
10.1200/JCO.22.02636.
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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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1200/JCO.22.02636 |
| Publisher version: | http://dx.doi.org/10.1200/jco.22.02636 |
| Language: | English |
| Additional information: | Copyright © 2023 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10186706 |
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