While dabrafenib as a single agent for 4 months did not prove to be effective as an adjuvant, targeted therapy has saved lives of melanoma patients. Now, there's this:
Long-Term Outcomes in Patients With BRAF V600-Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib. Long, Eroglu, Infante...Daud...Hamid...Sznol...Weber, et al. J Clin Oncol. 2017 Oct 9.
Patients and Methods: BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with greater than/= to 5 years of follow-up.
Results: As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed.
Conclusion: This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last greater than/= to 5 years in some patients with MM.
SO....we already knew that BRAF/MEK combined was much better than BRAFi alone...again evidenced here. With the combo there was 30% survival at 4 years, 28% at 5 years. Also with the combo, progression free survival was 13% at both the 4 and 5 year mark. Greater overall survival ocurred when patients started with a low baseline LDH level and fewer organ sites with mets (points that are true in immunotherapy as well).
While only about 1/2 of melanoma patients are BRAF positive, and thereby have BRAF/MEK as a viable treatment option, this is still good news. Melanoma's ability to mutate and work around the positive effects of BRAF treatment remains a fight. As noted in this report: Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS where:
Generally, prior studies of BRAF/MEK combos demonstrate about a 12 month PFS. This combo showed a PFS of 14.9 months. Objective response rate was 63% with the comb0. There was an ORR of 51% to encorafenib alone. Objective response rates to BRAF/MEK combo's in other studies have ranged from 48-70%, depending. OS data for encorafenib/binimetinib has not yet been reported. OS in most other BRAF/MEK combo's is around 2 years.
It is heartening to see in this latest report that there are those among the BRAF positive melanoma patients who can maintain responses at 5 years. Great thanks and admiration to Dick K and Stevie (among others) who pushed this envelope!!! - love, c
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