Second-Line Dovitinib Shows Some Activity in FGFR2-Mutant and FGFR2-Nonmutant Advanced Endometrial Cancer
In a phase II study reported in The Lancet Oncology, Konecny et al found that the multi–tyrosine kinase inhibitor dovitinib appeared to delay progression in some patients as second-line treatment in fibroblast growth factor receptor 2 (FGFR2)-mutant and -nonmutant advanced or metastatic endometrial cancer. However, the treatment effects did not meet prespecified criteria for continuing enrollment in the study. Activating FGFR2 mutations are found in 10% to 16% of primary endometrial cancers. Dovitinib inhibits FGFRs, VEGF receptors, PDGFR-β, and c-KIT.
Study Details
In the study, women with progressive disease after first-line chemotherapy were grouped according to FGFR2 mutation status and given oral dovitinib at 500 mg per day on a 5-days-on/2-days-off schedule until disease progression or unacceptable toxicity. The primary endpoint was proportion of patients in each group who were progression-free at 18 weeks; for each group, the second stage of the trial (enrollment of 20 additional patients) could proceed if ≥ 8 of the first 20 treated patients were progression-free at 18 weeks.
Efficacy
Between February 2012 and December 2013, 22 patients were enrolled in the FGFR2-mutant group and 31 patients in the FGFR2-nonmutant group. Overall, seven patients in the mutant group (31.8%, 95% confidence interval [CI] = 13.9%–54.9%) and nine in the nonmutant group (29.0%, 95% CI = 14.2%–48.0%) were progression-free at 18 weeks. However, neither group proceeded to stage 2, since progression-free status at 18 weeks was achieved in 7 (35%) of the first 20 mutant group patients and in 5 (25%) of the first 20 nonmutant group patients.
Adverse Events
The most common adverse events of any grade considered related to study treatment were diarrhea (67%), vomiting (64%), nausea (62%), and fatigue (44%), with the most common grade 3 or 4 events being hypertension (17%) and diarrhea (9%). The most common serious adverse events considered related to treatment were pulmonary embolism (8%), vomiting (8%), dehydration (6%), and diarrhea (6%). One death, due to cardiac arrest and pulmonary embolism, was considered treatment related.
The investigators concluded: “Second-line dovitinib in FGFR2[-mutant] and FGFR2[-nonmutant] advanced or metastatic endometrial cancer had single-agent activity, although it did not reach the prespecified study criteria. Observed treatment effects seemed independent of FGFR2 mutation status. These data should be considered exploratory and additional studies are needed.”
Gottfried E. Konecny, MD, of University of California Los Angeles, is the corresponding author for The Lancet Oncology article.
The study was funded by Novartis Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
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