Trastuzumab and Pertuzumab in patients with non-breast/gastroesophageal HER2 amplified tumors: Results from the NCI–MATCH ECOG–ACRIN Trial (EAY131) Subprotocol J

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dc.contributor.authorConnolly, Roisin M.en
dc.contributor.authorWang, Victoriaen
dc.contributor.authorHyman, David M.en
dc.contributor.authorGrivas, Petrosen
dc.contributor.authorMitchell, Edith P.en
dc.contributor.authorWright, John J.en
dc.contributor.authorSharon, Eladen
dc.contributor.authorGray, Robert J.en
dc.contributor.authorMcShane, Lisa M.en
dc.contributor.authorRubinstein, Larry V.en
dc.contributor.authorPatton, David R.en
dc.contributor.authorWilliams, P. Mickeyen
dc.contributor.authorHamilton, Stanley R.en
dc.contributor.authorWang, Jueen
dc.contributor.authorWisinski, Kari B.en
dc.contributor.authorTricoli, James V.en
dc.contributor.authorConley, Barbara A.en
dc.contributor.authorHarris, Lyndsay N.en
dc.contributor.authorArteaga, Carlos L.en
dc.contributor.authorO'Dwyer, Peter J.en
dc.contributor.authorChen, Alice P.en
dc.contributor.authorFlaherty, Keith T.en
dc.contributor.funderNational Cancer Instituteen
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2025-01-08T16:36:09Z
dc.date.available2025-01-08T16:36:09Z
dc.date.issued2024-04-01en
dc.description.abstractPurpose: NCI–MATCH assigned patients with advanced cancer and progression on prior treatment, based on genomic alterations in pretreatment tumor tissue. Arm J (EAY131-J) evaluated the combination of trastuzumab/pertuzumab (HP) across HER2-amplified tumors. Patients and Methods: Eligible patients had high levels of HER2 amplification [copy number (CN) ≥7] detected by central next-generation sequencing (NGS) or through NCI-designated laboratories. Patients with breast/gastroesophageal adenocarcinoma and those who received prior HER2-directed therapy were excluded. Enrollment of patients with colorectal cancer was capped at 4 based on emerging data. Patients received HP IV Q3 weeks until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Thirty-five patients were enrolled, with 25 included in the primary efficacy analysis (CN ≥7 confirmed by a central lab, median CN = 28). Median age was 66 (range, 31–80), and half of all patients had ≥3 prior therapies (range, 1–11). The confirmed ORR was 12% [3/25 partial responses (colorectal, cholangiocarcinoma, urothelial cancers), 90% confidence interval (CI) 3.4%–28.2%]. There was one additional partial response (urothelial cancer) in a patient with an unconfirmed ERBB2 copy number. Median PFS was 3.3 months (90% CI 2.0–4.1), and median OS 9.4 months (90% CI 5.0–18.9). Treatment-emergent adverse events were consistent with prior studies. There was no association between HER2 CN and response. Conclusions: HP was active in a selection of HER2-amplified tumors (non-breast/gastroesophageal) but did not meet the predefined efficacy benchmark. Additional strategies targeting HER2 and potential resistance pathways are warranted, especially in rare tumors.en
dc.description.sponsorshipNational Institutes of Health (U10CA180820; U10CA180794; UG1CA233302; UG1CA233180; UG1CA233341; UG1CA233196; UG1CA233290; UG1CA233328; UG1CA233277; U10CA180888)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationConnolly, R. M., Wang, V., Hyman, D. M., Grivas, P., Mitchell, E. P., Wright, J. J., Sharon, E., Gray, R. J., McShane, L. M., Rubinstein, L. V., Patton, D. R., Williams, P. M., Hamilton, S. R., Wang, J., Wisinski, K. B., Tricoli, J. V., Conley, B. A., Harris, L. N., Arteaga, C. L., O’Dwyer, P. J., Chen, A. P. and Flaherty, K. T. (2024) 'Trastuzumab and Pertuzumab in patients with non-breast/gastroesophageal HER2 amplified tumors: Results from the NCI–MATCH ECOG–ACRIN Trial (EAY131) Subprotocol J', Clinical Cancer Research, 30(7), pp.1273-1280. https://doi.org/10.1158/1078-0432.CCR-23-0633en
dc.identifier.doi10.1158/1078-0432.CCR-23-0633en
dc.identifier.eissn1557-3265en
dc.identifier.endpage1280en
dc.identifier.issn1078-0432en
dc.identifier.issued7en
dc.identifier.journaltitleClinical Cancer Researchen
dc.identifier.startpage1273en
dc.identifier.urihttps://hdl.handle.net/10468/16796
dc.identifier.volume30en
dc.language.isoenen
dc.publisherAmerican Associaton for Cancer Researchen
dc.relation.ispartofClinical Cancer Researchen
dc.rights© 2024, American Association for Cancer Research.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectAdvanced malignancyen
dc.subjectHER2en
dc.subjectTrastuzumaben
dc.subjectPertuzumaben
dc.titleTrastuzumab and Pertuzumab in patients with non-breast/gastroesophageal HER2 amplified tumors: Results from the NCI–MATCH ECOG–ACRIN Trial (EAY131) Subprotocol Jen
dc.typeArticle (peer-reviewed)en
oaire.citation.issue7en
oaire.citation.volume30en
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