Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201).

Autor:	Luke JJ; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. lukejj@upmc.edu., Olson DJ; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Allred JB; Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota., Strand CA; Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota., Bao R; Center for Research Informatics, University of Chicago, Chicago, Illinois.; Department of Pediatrics, University of Chicago, Chicago, Illinois., Zha Y; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Carll T; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Labadie BW; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Bastos BR; Miami Cancer Institute-Baptist Health South Florida, Miami, Florida., Butler MO; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Hogg D; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Munster PN; University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California., Schwartz GK; Columbia University Herbert Irving Comprehensive Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Feb 15; Vol. 26 (4), pp. 804-811. Date of Electronic Publication: 2019 Sep 26.
DOI:	10.1158/1078-0432.CCR-19-1223
Abstrakt:	Purpose: The surface receptor MET is highly expressed on primary uveal melanoma; MET inhibitors demonstrated early clinical signals of efficacy in slowing uveal melanoma growth. The primary objective of our study was to compare the progression-free survival rate at 4 months (PFS4) of patients with uveal melanoma treated with cabozantinib or chemotherapy. Patients and Methods: Patients with metastatic uveal melanoma and RECIST measurable disease were randomized 2:1 to receive either cabozantinib (arm 1) versus temozolomide or dacarbazine (arm 2) with restaging imaging every two cycles. Cross-over from arm 2 to cabozantinib after progression was allowed (arm 2X). Available tumor specimens were analyzed by whole-exome sequencing (WES) and results were correlated with outcome. Results: Forty-six eligible patients were accrued with 31, 15, and 9 in arms 1, 2, and 2X, respectively. Median lines of prior therapy, including hepatic embolization, were two. Rates of PFS4 in arm 1 and arm 2 were 32.3% and 26.7% ( P = 0.35), respectively, with median PFS time of 60 and 59 days ( P = 0.964; HR = 0.99). Median overall survival (OS) was 6.4 months and 7.3 months ( P = 0.580; HR = 1.21), respectively. Grade 3-4 Common Terminology Criteria for Adverse Events were present in 61.3%, 46.7%, and 37.5% in arms 1, 2, and 2X, respectively. WES demonstrated a mean tumor mutational burden of 1.53 mutations/Mb and did not separate OS ≤ or >1 year ( P = 0.14). Known mutations were identified by WES and novel mutations were nominated. Conclusions: MET/VEGFR blockade with cabozantinib demonstrated no improvement in PFS but an increase in toxicity relative to temozolomide/dacarbazine in metastatic uveal melanoma. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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