Combi-D: Quality of Life (Qol) Impact of the Combination of Dabrafenib and Trametinib (D + T) Versus Dabrafenib Monotherapy (D) in Patients with Braf V600E/K Unresectable or Metastatic Melanoma in a Phase III Trial

Abstract

ABSTRACT Aim: COMBI-d is a double-blinded, randomized phase III study (NCT01584648) that demonstrated a statistically significant improvement in PFS (HR = 0.75; 95% CI 0.57–0.99; P = 0.035), and overall response rate (ORR) (67% vs. 51%; P = 0.0015) for D + T vs. D in patients with BRAF V600E/K unresectable or metastatic melanoma. This analysis presents the impact of treatments on QOL. Methods: QOL was assessed using the EORTC QLQ-C30, a self-reporting generic cancer questionnaire (completed at baseline, during study treatment, at progression and post-progression). It assesses various dimensions, including global health/QOL, functional status and symptom impact. A mixed-model, repeated measures analyses of covariance assessed differences between arms. Results: Questionnaire completion rates (as % of available subjects) were >90% at baseline and at weeks 8, 16, 24 and 32, and 71% at progression. At baseline, patients in both treatment arms reported comparable scores for all dimensions. The global health/QOL dimension was consistently better (significantly at weeks 8, 16 and 24) for patients receiving D + T compared with those receiving D during treatment and at progression. For functional dimensions (physical, social, role, emotional, and cognitive functioning) the majority of scores trended in favor of patients receiving D + T. In terms of symptom impact, pain scores were significantly improved and clinically meaningful (6–13 point difference) for patients receiving D + T compared with those receiving D for all follow-up assessments. For other symptom dimensions (nausea and vomiting, diarrhea, dyspnea and constipation), scores trended in favor of D. Dimension Change from baseline to week/visit 8 16 24 32 Progression Global health/QOL +* +* +* + + Functioning Cognitive + – – – – Emotional + + + + + Physical + +* + + + Role + + +* +* + Social + + + +* + Symptoms Appetite Loss – – + – + Constipation – – – – + Diarrhea – – – – – Dyspnea – – – – – Fatigue – + + + + Insomnia + + + + + Nausea and vomiting – –* –* – – Pain +* +* +* +* +* + favors D + T;–favors D; *P Conclusions: In addition to the superior PFS and ORR of D + T vs. D, this analysis demonstrates that the combination provides further patient benefit based on global health/QOL and pain improvements. Disclosure: D. Schadendorf: D.S. has received case money from GSK. D.S. has received personal fees and non-financial support from GSK, Roche, Novartis, Amgen, Merck/MSD and received a grant from Merck/MSD M.M. Amonkar: M.M.A is an employee of GSK and owns stock in GSK; H. Gogas: H.G. has received personal fees from BMS, Roch, Merck, Novartis and Amgen; J.-. Grob: J-J.G. received personal fees from GSK, Roche, NMS, Merck, Celgene and Novartis; C. Garbe: C.G. has received grants and personal fees from GSK and Roche. C.G. has received personal fees from MSD, Novartis and Philogen; C. Lebbe: C.L. has received personal fees for participation in advisory boards from GSK, Roche, BMS and Novartis; J. Larkin: J.L. has received grants and personal fees from Novartis and Pfizer. J.L. has received personal fees from BMS and GSK; V. Chiarion-Sileni: V.C-S. has received fees from GSK, BMS and Roche for participating in advisory boards; M. Millward: M.M. has received clinical trial payments from GSK. M.M. has received personal fees for participating in an advisory board; A. Arance: A.A. has received a grant, personal fees and non-financial support from GSK. A.A. has received a grant and personal fees from Roche. A.A. has received personal fees from BMS; M. Casey: M.C. is an employee of GSK and owns stock in GSK; D.J. Demarini: D.J.DeM. is an employee of GSK. D.J.DeM. has an issued patent for Pharmaceutical Composition Containing Trametinib. D.J.DeM. has a patent pending for Combinations of Mekinist + gemcitabine; J. Irani: J.I. is an employee of GSK; G. Aktan: G.A. is an employee of GSK. G.A. owns stock in GSK; G.V. Long: Trial conducted at G.V.L.'s institution, sponsored by GSK. G.V.L. has received personal fees as a consultant advisor for Roche, GSK and Novartis. All other authors have declared no conflicts of interest.