CNS metastases in patients with MET exon 14-altered lung cancers and outcomes with crizotinib Journal Article


Authors: Offin, M.; Luo, J.; Guo, R.; Lyo, J. K.; Falcon, C.; Dienstag, J.; Wilkins, O.; Chang, J.; Rudin, C. M.; Riely, G.; Rekhtman, N.; Arcila, M. E.; Heller, G.; Ladanyi, M.; Li, B. T.; Kris, M. G.; Paik, P.; Drilon, A.
Article Title: CNS metastases in patients with MET exon 14-altered lung cancers and outcomes with crizotinib
Abstract: PURPOSE Although MET exon 14 (METex14)–altered lung cancers were first identified more than a decade and a half ago, the frequency of CNS metastatic disease remains poorly defined. Furthermore, the seminal trial of crizotinib in these patients (PROFILE 1001) did not report patterns of CNS response or progression. PATIENTS AND METHODS Patients with pathologically confirmed, advanced non–small-cell lung cancers (NSCLC) harboring a METex14 alteration by targeted DNA/RNA sequencing were studied. The incidence of brain metastases and the outcomes of MET inhibition with crizotinib were analyzed. RESULTS Eighty-three patients with METex14-altered metastatic NSCLC were identified. The incidence of CNS metastases at diagnosis was 17% (95% CI, 10% to 27%). The lifetime incidence was 36% (95% CI, 26% to 47%); 83% of patients had parenchymal disease, and 17% had leptomeningeal disease. The probability of having brain metastasis at 1, 2, and 3 years was 24%, 35%, and 38%, respectively. Fifty-four patients received crizotinib. The median time to radiologic CNS progression was 5.8 months (range, 3.7-20.0 months). Patterns of crizotinib progression were as follows: intracranial only in 10% of patients, intracranial and extracranial in 12%, and extracranial only in 78%. In patients with brain metastases before treatment, the median time on crizotinib was 7.5 months (range, 7.2-11.7 months). CONCLUSION CNS metastases, including leptomeningeal disease, occurred in more than a third of patients with METex14-altered lung cancers. In crizotinib-treated patients with or without CNS metastases, CNS failure was seen in less than a quarter of patients on progression. © 2020 by American Society of Clinical Oncology
Journal Title: JCO Precision Oncology
Volume: 4
ISSN: 2473-4284
Publisher: American Society of Clinical Oncology  
Date Published: 2020-07-27
Start Page: 871
End Page: 876
Language: English
DOI: 10.1200/po.20.00098
PROVIDER: scopus
PMCID: PMC7446485
PUBMED: 32923895
DOI/URL:
Notes: Article -- Export Date: 1 October 2020 -- Source: Scopus
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MSK Authors
  1. John Kyungjin Lyo
    39 Lyo
  2. Natasha Rekhtman
    434 Rekhtman
  3. Glenn Heller
    399 Heller
  4. Marc Ladanyi
    1332 Ladanyi
  5. Gregory J Riely
    603 Riely
  6. Paul K Paik
    256 Paik
  7. Maria Eugenia Arcila
    669 Arcila
  8. Mark Kris
    871 Kris
  9. Alexander Edward Drilon
    635 Drilon
  10. Charles Rudin
    494 Rudin
  11. Jason Chih-Peng Chang
    142 Chang
  12. Bob Tingkan Li
    279 Li
  13. Michael David Offin
    172 Offin
  14. Robin Guo
    24 Guo
  15. Jia Luo
    27 Luo
  16. Christina Jade Falcon
    45 Falcon