Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET–rearranged lung cancers Journal Article


Authors: Drilon, A.; Lin, J. J.; Filleron, T.; Ni, A.; Milia, J.; Bergagnini, I.; Hatzoglou, V.; Velcheti, V.; Offin, M.; Li, B.; Carbone, D. P.; Besse, B.; Mok, T.; Awad, M. M.; Wolf, J.; Owen, D.; Camidge, D. R.; Riely, G. J.; Peled, N.; Kris, M. G.; Mazieres, J.; Gainor, J. F.; Gautschi, O.
Article Title: Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET–rearranged lung cancers
Abstract: Introduction: In ret proto-oncogene (RET)–rearranged lung cancers, data on the frequency of brain metastases and, in particular, the outcomes of multikinase inhibitor therapy in patients with intracranial disease are not well characterized. Methods: A global, multi-institutional registry (cohort A, n = 114) and a bi-institutional data set (cohort B, n = 71) of RET-rearranged lung cancer patients were analyzed. Patients were eligible if they had stage IV lung cancers harboring a RET rearrangement by local testing. The incidence of brain metastases and outcomes with multikinase inhibitor therapy were determined. Results: The frequency of brain metastases at the time of diagnosis of stage IV disease was 25% (95% confidence interval [CI]: 18%–32%) in all patients from both cohorts. The lifetime prevalence of brain metastasis in stage IV disease was 46% (95% CI: 34%–58%) in patients for whom longitudinal data was available. The cumulative incidence of brain metastases was significantly different (p = 0.0039) between RET-, ROS1-, and ALK receptor tyrosine kinase (ALK)–rearranged lung cancers, with RET intermediate between the other two groups. Although intracranial response data was not available in cohort A, the median progression-free survival of multikinase inhibitor therapy (cabozantinib, vandetanib, or sunitinib) in patients with brain metastases was 2.1 months (95% CI: 1.3–2.9 months, n = 10). In cohort B, an intracranial response was observed in 2 of 11 patients (18%) treated with cabozantinib, vandetanib (± everolimus), ponatinib, or alectinib; the median overall progression-free survival (intracranial and extracranial) was 3.9 months (95% CI: 2.0–4.9 months). Conclusions: Brain metastases occur frequently in RET-rearranged lung cancers, and outcomes with multikinase inhibitor therapy in general are suboptimal. Novel RET-directed targeted therapy strategies are needed. © 2018 International Association for the Study of Lung Cancer
Keywords: brain metastases; ret rearrangement; ret fusion; lung cancer cabozantinib; vandetanib multikinase inhibitor
Journal Title: Journal of Thoracic Oncology
Volume: 13
Issue: 10
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2018-10-01
Start Page: 1595
End Page: 1601
Language: English
DOI: 10.1016/j.jtho.2018.07.004
PROVIDER: scopus
PUBMED: 30017832
DOI/URL:
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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MSK Authors
  1. Gregory J Riely
    378 Riely
  2. Mark Kris
    671 Kris
  3. Alexander Edward Drilon
    175 Drilon
  4. Bob Tingkan Li
    76 Li
  5. Ai   Ni
    66 Ni
  6. Michael David Offin
    28 Offin