Four months of Dabrafenib as adjuvant ~ not a good plan

As most of you are probably tired of hearing, I've been yelling about the need for adjuvant treatments for patients with Stage III and IV melanoma, rendered NED through surgery and/or radiation for years!  We know there are many options that work (ipi and nivo, to start) and some that don't (interferon).  There is excellent data showing the effectiveness of targeted therapy (Dabrafenib with Trametinib) as adjuvant as well.  Here's a link to a zillion articles addressing all those options:  Adjuvant treatments for melanoma  Now there's this:

Four-month course of adjuvant dabrafenib in patients with surgically resected stage IIIC melanoma characterized by a BRAFV600E/K mutation. Momtaz, Harding, Ariyan...Postow, Wolchok, Chapman. Oncotarget. eCollection 2017 Dec 1.

We tested the hypothesis that a 4-month course of adjuvant dabrafenib in stage IIIC BRAF-mutated melanoma would improve 2 year RFS from 24% to 51%, and that tumor-derived cell free DNA (cfDNA) in plasma would correlate with and predict recurrence.

Patients with stage IIIC BRAF V600E/K mutated melanoma who were free of disease after surgical resection received 4 months of adjuvant dabrafenib. Patients were evaluated with imaging at baseline, at the end of cycles 2, 4, 6, then every 3 months until disease relapse or 2 years, whichever came first. Serial blood samples were collected for evaluation of cfDNA at the same time.

21/23 patients enrolled were evaluable; 2 patients withdrew consent during the first week of treatment. The 2 year RFS was 28.6%. The estimated overall survival at 2 years was 78%. cfDNA detection had a 53% sensitivity in relapsing patients but cfDNA detection did not provide lead-time advantage over CT scanning.

A 4-month course of adjuvant dabrafenib did not result in a detectable improvement in 2-year RFS. cfDNA was less sensitive than standard CT imaging and did not provide a lead-time advantage in detecting relapse.

So, 23 peeps with Stage III, BRAF positive melanoma, were given the single agent dabrafenib for 4 months.  Unfortunately, it did not provide any "detectable improvement in 2-year recurrence free survival".  The thing that confuses me here is why researchers would even do this to patients!!!  We have known for many years now that when we COMBINE BRAF inhibitors WITH a MEK inhibitor patients have much fewer side effects (and therefore tolerate the treatment more easily) and simultaneously attain a much higher response rate with decreased rates of tumor work-around.  Why at this late date anyone would use Dabrafenib as a single agent is beyond me!!!  At any rate...now we 'know'!

Thanks ratties.  - c