Analysis of patient-reported outcomes by disease progression status in patients (pts) with BRAF V600–mutant metastatic melanoma in the COMBI-d and COMBI-v trials

Background

Dabrafenib (D) + trametinib (T) improved efficacy and better maintained health-related quality of life (HRQOL) vs BRAF inhibitor monotherapy in 2 phase 3 trials of pts with BRAF V600–mutant metastatic melanoma, COMBI-d (D + T vs D + placebo) and COMBI-v (D + T vs vemurafenib). Here, we examine the association of tumor response with HRQOL and symptom scores in COMBI-d and COMBI-v.

Methods

COMBI-d and COMBI-v are randomized, double-blind phase 3 trials in pts with unresectable BRAF V600–mutant metastatic melanoma. The EORTC QLQ-C30 was used to assess HRQOL and symptom scores at baseline and during treatment. Treatment arms in each study were pooled and analyzed by best response (complete response [CR]/partial response [PR] vs stable disease [SD]/progressive disease [PD]). Maximum improvement (MI) was defined as maximum increase from baseline in functional domains and maximum decrease in symptom scores. P values were calculated by 2-sample t test.

Results

In COMBI-d (N = 423; CR/PR, n = 256; SD/PD, n = 148) and COMBI-v (N = 704; CR/PR, n = 417; SD/PD, n = 250), completion rates allowed mean MI scores to be calculated for ≥ 90% of pts. In COMBI-d, pts with CR/PR had greater mean MI in HRQOL vs pts with SD/PD in the global health dimension (13.8 vs 7.5; P = .004) and all functional domains (role [10.2 vs 7.9; P = .425]; social [10.3 vs 6.2; P = .112]; emotional [15.4 vs 10.3; P = .018]; physical [6.0 vs 5.3; P = .664]; cognitive [4.9 vs 1.9; P = .070]). Pts with CR/PR also had greater MI in most symptom scores vs pts with SD/PD, including > 5-point improvements in pain (P = .034) and insomnia (P = .065). Similarly, in COMBI-v, pts with CR/PR had a greater mean MI vs pts with SD/PD in the global health dimension (12.9 vs 7.1; P = .001) and all functional domains (role [9.7 vs 8.3; P = .548]; social [10.1 vs 6.8; P = .134]; emotional [16.1 vs 10.3; P 

Conclusions

Pts with a response had a greater MI from baseline in HRQOL and symptom scores vs pts without a response, demonstrating the association between tumor shrinkage and HRQOL in COMBI-d and COMBI-v.

Clinical trial identification

NCT01597908; first received by clinicaltrials.gov on May 10, 2012 and NCT01584648; first received by clinicaltrials.gov on April 23, 2012

Legal entity responsible for the study

Supported by GlaxoSmithKline. Dabrafenib and trametinib are assets of Novartis AG as of 2 March 2015.

Funding

Supported by GlaxoSmithKline. Dabrafenib and trametinib are assets of Novartis AG as of 2 March 2015.

Disclosure

C. Robert: Consultancy: Novartis, Amgen, BMS, Merck, Roche Honoraria: Novartis, Amgen, BMS, Merck, Roche. D. Schadendorf: Consultancy, Honoraria, Speakers Bureau: Amgen, Novartis, Roche, BMS, MSD Merck, Pfizer Research Funding: BMS, MSD Merck Membership-Advisory Committee: Amgen, Novartis, Roche, BMS, MSD Merck, Pfizer, Array. G.V. Long: Consultancy: Roche, BMS, Merck, Amgen, Novartis Honoraria: BMS, Merck, Novartis. V. Chiarion-Sileni: Consultancy: Novartis, BMS Speakers Bureau: GSK, Novartis Membership on Board of Directors or Advisory Committee: GSK, Novartis, Roche, BMS, MSD. K. Flaherty: Consultancy: Novartis, Roche, Array, Lilly, Takeda Research Funding: Novartis. P. Nathan: Consultancy: Novartis Speakers Bureau: Novartis Membership on Board of Directors or Advisory Committee: Novartis. A. Ribas: Consultancy: Novartis, Merck, Pfizer, Roche Equity Ownership: Kite Pharma Honoraria: Novartis. M. Davies: Research Funding: Genentech/Roche, GSK, AstraZeneca, Sanofi-Aventis, Merck Membership on Board of Directors or Advisory Committee: Novartis, Genentech/Roche, GSK, Sanofi-Aventis, Vaccinex. J. Zhang: Employment: Novartis Equity Ownership: Stockholder. L. Chen: Employment: Novartis Equity Ownership: Novartis. B. Mookerjee: Employment: Novartis Equity Ownership: Novartis, GSK, Incyte, AstraZeneca. S. Redhu: Employment: Novartis. J.J. Grob: Consultancy: Novartis, GSK, Roche, Merck, BMS, Amgen. All other authors have declared no conflicts of interest.