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Dabrafenib plus trametinib improves health-related quality of life in metastatic melanoma
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The addition of trametinib to dabrafenib improved health-related quality of life and reduced pain in patients with BRAF V600-mutated metastatic melanoma, according to results of a randomized phase 3 study.
The combination of dabrafenib (Tafinlar, GlaxoSmithKline) and trametinib (Mekinist, GlaxoSmithKline) received accelerated approval from the FDA in 2014 based on the results of a phase 1/2 study that compared the combination with dabrafenib monotherapy. Results from a phase 3 trial later demonstrated significantly improved PFS and objective rate response with the combination vs. dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.
In the current analysis, Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen in Germany, and colleagues sought to evaluate the effect of the combination on health-related quality of life among patients treated in the phase 3 study.
Dirk Schadendorf
The analysis included 423 patients with historically resectable stage IIIC or stage IV melanoma with BRAF V600E or V600K mutations. Patients received 150 mg twice daily dabrafenib alone (n = 212) or with 2 mg daily trametinib (n = 211).
Researchers conducted health-related quality of life assessments using the EORTC Quality of Life Questionnaire-C30 at baseline, every 8 weeks until week 56, and every 12 weeks thereafter until disease progression. Health-related quality of life was comparable in each arm at baseline.
Patients who received dabrafenib and trametinib displayed improved health-related quality of life at weeks 8 (P = .049), 16 (P = .035) and 24 (P = .045) compared with patients in the dabrafenib monotherapy arm.
The combination was associated with significant improvements in physical functioning at weeks 16 and 40, role functioning at weeks 24 and 32, social functioning at weeks 32 and 40 and cognitive functioning at week 40. Clinically meaningful improvements occurred in role functioning at weeks 24, 32 and 40 and at disease progression; cognitive functioning at week 40; and social functioning at weeks 32 and 40.
The combination conferred statistically significant and clinically meaningful improvements in pain scores at all follow-up assessments (6- to 13-point improvement). However, symptom scores for nausea and vomiting, diarrhea, dyspnea and constipation trended in favor of dabrafenib monotherapy.
“In addition to clinical benefits, such as delayed progression, high tumor response rates and longer survival, [health-related quality of life] is an important consideration for patients with advanced melanoma, particularly as treatment is not curative in the majority of patients,” Schadendorf and colleagues wrote. “These data further support the clinical benefit that the combination of dabrafenib and trametinib compared with dabrafenib alone has shown in terms of improved PFS.” – by Cameron Kelsall
Disclosure: The study was funded by GlaxoSmithKline. Schadendorf reports research funding from and advisory roles with Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis and Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.
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