It was certainly good news when the FDA (FINALLY!!!) approved ipi as an adjuvant treatment for melanoma. And....it works! ASCO 2017: Ipi 3 mg vs 10 mg in advanced melanoma and as adjuvant
We also KNOW that anti-PD-1 works EVEN BETTER, with fewer side effects, as an adjuvant treatment in melanoma. The trial that I and my fellow ratties started in 2010 proved that...and so have other studies since: Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!!
We also KNOW that BRAF/MEK inhibitors are extremely effective as an adjuvant therapy in patients with BRAF positive melanoma: 2016: Straight Outta Boston!!! Latest melanoma research ~
One abstract included in that link notes:
Stage IIIB/C treated with adjuvant BRAFi = 100% 6 month survival vs 28.6% with standard care!!!
Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. Long, Hauschild, Santinami, et al. N Engl J Med. 2017 Sep 10.
Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations.
In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety.
At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group. The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group, but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma.
Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects.
Relapse free survival...58% with treatment, 39% with placebo! Sounds good to me...of course you have to be BRAF positive....but it's something!!!
Now this is something "new"....and VERY old!!! Remember this post: Immunotherapy....The Original Super Heroes and Ratties!!!! When you talk about CpG-B - Coley's toxin comes to mind, who, in the 1890's, injected bacteria into tumors and found that they would GO AWAY!!! In 1983 an underlying DNA component of the bacteria, responsible for the effect, was discovered. And in 1995, the specific DNA molecules (CpG) were found to be the component that specifically stimulated the immune response, with the B group in particular, causing B cell and monocyte maturation. And since some of the patients were also given GM-CSF in the study below, here's a reminder about what that is: Sargramostim ~ aka GM-CSF or leukine (and other related posts) Here's the latest:
Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I-II Melanoma: Data from Two Randomized Phase II Trials. Koster, Van den Hout, Sluijter, et al. Clin Cancer Res. 2017 Oct 1.
Although risk of recurrence after surgical removal of clinical stage I-II melanoma is considerable, there is no adjuvant therapy with proven efficacy. Here, we provide clinical evidence that a local conditioning regimen, aimed at immunologic arming of the tumor-draining lymph nodes, may provide durable protection against disease recurrence (median follow-up, 88.8 months).
And there's this.... Here, CancerVax (canvaxin) was given along with BCG.