Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: Results from a phase II basket trial Journal Article


Authors: Li, B. T.; Shen, R. L.; Buonocore, D.; Olah, Z. T.; Ni, A.; Ginsberg, M. S.; Ulaner, G. A.; Offin, M.; Feldman, D.; Hembrough, T.; Cecchi, F.; Schwartz, S.; Pavlakis, N.; Clarke, S.; Won, H. H.; Brzostowski, E. B.; Riely, G. J.; Solit, D. B.; Hyman, D. M.; Drilon, A.; Rudin, C. M.; Berger, M. F.; Baselga, J.; Scaltriti, M.; Arcila, M. E.; Kris, M. G.
Article Title: Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: Results from a phase II basket trial
Abstract: PurposeHuman epidermal growth factor receptor 2 (HER2, ERBB2)-activating mutations occur in 2% of lung cancers. We assessed the activity of ado-trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, in a cohort of patients with HER2-mutant lung cancers as part of a phase II basket trial.Patients and MethodsPatients received ado-trastuzumab emtansine at 3.6 mg/kg intravenously every 3 weeks until progression. The primary end point was overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A Simon two-stage optimal design was used. Other end points included progression-free survival and toxicity. HER2 testing was performed on tumor tissue by next generation sequencing, fluorescence in situ hybridization, immunohistochemistry, and protein mass spectrometry.ResultsWe treated 18 patients with advanced HER2-mutant lung adenocarcinomas. The median number of prior systemic therapies was two (range, zero to four prior therapies). The partial response rate was 44% (95% CI, 22% to 69%), meeting the primary end point. Responses were seen in patients with HER2 exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains. Concurrent HER2 amplification was observed in two patients. HER2 immunohistochemistry ranged from 0 to 2+ and did not predict response, and responders had low HER2 protein expression measured by mass spectrometry. The median progression-free survival was 5 months (95% CI, 3 to 9 months). Toxicities included grade 1 or 2 infusion reactions, thrombocytopenia, and elevated hepatic transaminases. No patient stopped therapy as a result of toxicity or died on study.ConclusionAdo-trastuzumab emtansine is an active agent in patients with HER2-mutant lung cancers. This is the first positive trial in this molecular subset of lung cancers. Further use and study of this agent are warranted.
Keywords: cisplatin; gemcitabine; chemotherapy; oncology; carcinoma; therapy; breast-cancer; vemurafenib; her2 mutations; kinase mutations
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 24
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-08-20
Start Page: 2532
End Page: 2537
Language: English
ACCESSION: WOS:000445668100009
DOI: 10.1200/jco.2018.77.9777
PROVIDER: wos
PUBMED: 29989854
PMCID: PMC6366814
Notes: Article -- Source: Wos
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MSK Authors
  1. Gary Ulaner
    114 Ulaner
  2. Michelle S Ginsberg
    176 Ginsberg
  3. David Solit
    544 Solit
  4. Ronglai Shen
    143 Shen
  5. Gregory J Riely
    417 Riely
  6. David Hyman
    302 Hyman
  7. Michael Forman Berger
    497 Berger
  8. Maria Eugenia Arcila
    459 Arcila
  9. Mark Kris
    713 Kris
  10. Alexander Edward Drilon
    248 Drilon
  11. Helen Hyeong-Eun Won
    90 Won
  12. Jose T Baselga
    462 Baselga
  13. Maurizio Scaltriti
    125 Scaltriti
  14. Charles Rudin
    229 Rudin
  15. Bob Tingkan Li
    99 Li
  16. Ai   Ni
    82 Ni
  17. Michael David Offin
    43 Offin
  18. Zachary T Olah
    5 Olah