Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: Results from the NCI-MATCH trial (EAY131) subprotocol Q Journal Article


Authors: Jhaveri, K. L.; Wang, X. V.; Makker, V.; Luoh, S. W.; Mitchell, E. P.; Zwiebel, J. A.; Sharon, E.; Gray, R. J.; Li, S.; McShane, L. M.; Rubinstein, L. V.; Patton, D.; Williams, P. M.; Hamilton, S. R.; Conley, B. A.; Arteaga, C. L.; Harris, L. N.; O'Dwyer, P. J.; Chen, A. P.; Flaherty, K. T.
Article Title: Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: Results from the NCI-MATCH trial (EAY131) subprotocol Q
Abstract: Background: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. Methods: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq (TM) (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. Results: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. Conclusion: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.
Keywords: survival; amplification; validation; therapy; solid tumors; her2; plus; guideline; t-dm1; cancer; her2-amplified; ngs; nci-match; american-pathologists
Journal Title: Annals of Oncology
Volume: 30
Issue: 11
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2019-11-01
Start Page: 1821
End Page: 1830
Language: English
ACCESSION: WOS:000507594800018
DOI: 10.1093/annonc/mdz291
PROVIDER: wos
PUBMED: 31504139
PMCID: PMC6927318
Notes: Article -- Source: Wos
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MSK Authors
  1. Vicky Makker
    108 Makker
  2. Komal Lachhman Jhaveri
    78 Jhaveri