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|Ref Type||Journal Article|
|Authors||Wakelee HA, Gettinger S, Engelman J, Jänne PA, West H, Subramaniam DS, Leach J, Wax M, Yaron Y, Miles DR, Lara PN|
|Title||A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.|
|Journal||Cancer chemotherapy and pharmacology|
|Date||2017 Mar 28|
|Abstract Text||Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR).Sixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa.Despite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||lung non-small cell carcinoma||not applicable||Cabozantinib + Erlotinib||Phase Ib/II||Actionable||In a Phase Ib/II trial, Cometriq (cabozantinib) and Tarceva (erlotinib) combination treatment resulted in no response (0/13) in patients with non-small cell lung carcinoma that had progressed during treatment with Tarceva (erlotinib) in Phase II, despite an objective response rate of 8.2% (5/61) in Phase I (PMID: 28352985).||28352985|
|Unknown unknown||lung non-small cell carcinoma||not applicable||Cabozantinib||Phase Ib/II||Actionable||In a Phase Ib/II trial, Cometriq (cabozantinib) treatment resulted in partial response in 6.7% (1/15) of patients with non-small cell lung carcinoma that had progressed during treatment with Tarceva (erlotinib), with a median progression free survival of 1.9 months (PMID: 28352985).||28352985|