Real‐world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced melanoma

Abstract

We conducted a retrospective investigation of the efficacy and safety of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced melanoma in real‐world clinical practise. The study analyzed 50 patients who received dabrafenib and trametinib combination therapy for BRAF V600 mutation‐positive advanced melanoma in our hospital (26 men and 24 women, aged 21–86 years, inclusive; median age, 53 years). The response rate was 72.3%, with complete response (CR) achieved in eight cases (17.0%), partial response in 26 (55.3%), stable disease in nine (19.1%) and progressive disease in four (8.5%). Median progression‐free survival (PFS) was 12 months, and median overall survival (OS) was 23 months. Disease progression occurred in 29 of the 50 patients during the study period, and 25 patients died. Baseline lactate dehydrogenase and the number of organs with metastasis were important predictive factors for PFS and OS, and CR to combination therapy was a predictive factor for long‐term remission. Adverse events occurred in 88% of cases; 16% were grade 3 or worse. The adverse events observed in 50% of more of patients were rash (56%) and pyrexia (52%). The efficacy of dabrafenib and trametinib combination therapy in Japanese patients was similar to that reported in global studies, and the same adverse events were generally reported; however, rash tended to occur more frequently in the patients in our study.

Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial

“…Multivariate analysis of baseline factors demonstrated that LDH levels and the number of metastatic sites were significantly associated with PFS and OS, corroborating previous randomized trials in Caucasian melanoma patients ( 9 , 25 , 26 ).…”

“…Therefore, patients with fewer lines of previous therapy, no previous immunotherapy, fewer metastatic organ sites and no visceral disease might gain more survival benefits from the combined regimen. Furthermore, while analyzing survival in patients with different tumor response in this trial, optimal outcomes were observed in individuals who achieved CR, confirming previous analyses ( 25 , 26 ).…”

Early Experience with Dabrafenib–Trametinib Combination in Patients with BRAF-Mutated Malignant Melanoma—A Single-Center Experience

“…16 The response rate of our study population was 66%, which was almost similar to 67% in clinical trial settings 16 and 72% from the Japanese study. 17 At a median follow-up of 23 months, the median PFS of the cohort of our patients was 9.3 months. It is almost similar to the updated analysis of the pivotal landmark trial where it was 11.1 months.…”

Efficacy, safety and factors associated with disease progression in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: An open label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib

“…Among BRAF inhibitor-naïve patients, the ORR was 67.3% and median PFS was 7.5 months. In a Japanese study [19] that included only 50 patients, the response rate was 72.3%, with CR achieved in 8 cases (17.0%), PR in 26 (55.3%), SD in 9 (19.1%) and PD in 4 (8.5%).…”