Trastuzumab and pertuzumab in patients with non-breast/gastroesophageal HER2-amplified tumors: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol J Journal Article
| Authors: | Connolly, 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.; Flaherty, K. T. |
| Article Title: | Trastuzumab and pertuzumab in patients with non-breast/gastroesophageal HER2-amplified tumors: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol J |
| Abstract: | Purpose: 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. © 2024 American Association for Cancer Research. |
| Keywords: | adult; clinical article; controlled study; aged; unclassified drug; gene mutation; overall survival; clinical trial; fatigue; histopathology; diarrhea; hypertension; hypophosphatemia; antineoplastic agent; colorectal cancer; metabolism; progression free survival; phase 2 clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor; epidermal growth factor receptor 2; creatinine; pathology; breast neoplasms; monoclonal antibody; abdominal pain; dyspnea; loading drug dose; hypoxia; hypotension; heart failure; breast tumor; cancer registry; receptor, erbb-2; bile duct carcinoma; echocardiography; trastuzumab; esophagus cancer; heart left ventricle ejection fraction; hepatobiliary disease; disease exacerbation; human epidermal growth factor receptor 2; pertuzumab; progression-free survival; colorectal adenocarcinoma; response evaluation criteria in solid tumors; antibodies, monoclonal, humanized; Common Terminology Criteria for Adverse Events; high throughput sequencing; infusion related reaction; very elderly; humans; human; male; female; article; ecog performance status; molecular fingerprinting; data availability |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-04-01 |
| Start Page: | 1273 |
| End Page: | 1280 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-0633 |
| PUBMED: | 38433347 |
| PROVIDER: | scopus |
| PMCID: | PMC10984755 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
