ASCO 2016 - Two Adjuvant studies for Stage III/IV - with interferon vs pembro vs ipi - still recruiting

Knowing, as we do, that ALL melanoma therapies work best with the lowest possible tumor burden and as a person who was Stage IV post brain and lung mets in 2010, rendered NED after having my brain zapped and upper lobe of my lung removed, I was the lucky beneficiary of an adjuvant nivo trial in which I was dosed for 2 1/2 years and remain NED today!!!  (See my trial's results and other reports on adjuvant treatment below.)  Therefore, all I can say about this is:  It's about damn time and they need to leave interferon out of the mix!!!!!!!!!!!  Just say'n! Though a person looking to participate in this study was told...and passed on to me...that if you got the interferon arm, they would allow you to move off that to either ipi or pembro....cause the ipi arm did, in fact, get included.

SWOG S1404: A phase III randomized trial comparing standard of care adjuvant therapy to pembrolizumab in patients with high risk resected melanoma.  ASCO 2016.  # e21032.  J Clin Oncol 34, 2016.  Grossmann, Othus, Tarhini, et al.

Background: With the recent FDA approval of ipilimumab, the treatment options available to patients with high risk resected melanoma has changed. Now, reasonable treatment choices include high dose interferon, ipilimumab dosed at 10 mg/kg, and pegylated interferon. Among these treatments, HDI remains the only treatment to show an overall survival benefit in randomized trials. With the high response rates, and relatively low toxicity profile seen in the treatment of Stage IV melanoma with pembrolizumab, investigation of this agent in stage III patients is a critical priority. S1404 is a randomized trial comparing standard of care HDI to pembrolizumab in patients at high risk for recurrence and death after surgery. Methods: Patients age 18 or greater with Stages IIIA(N2), IIIB, IIIC and IV (M1a, b and c) are eligible. Patients with brain metastasis will be excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel lymph node positive disease. Prior therapy with PD-1 blockade or interferon are not allowed. Two treatment arms are assigned based on stratification by stage and PD-L1 staining status (positive vs negative vs unknown). Patients (n = 1,378) will be randomized 1:1 to either 1) interferon Alfa-2b 20 MU/m2/days 1-5 weeks 1-4, followed by Interferon Alfa-2b 10 MU/m2/d SC days 1,3,5weeks 5 -52, or 2) pembrolizumab 200 mg day 1, q 3 weeks for 52 weeks. Efficacy will be measured in terms of both overall survival and relapse free survival, with interim analyses planned for both endpoints at 50% OS information. Safety, pharmacokinetics, and quality of life data will also be studied. Results: As of January 29, 2016, 36 sites are registered, 29 patients are in screening, and 13 patients randomized. An amendment to include 10 mg/kg ipilimumab as a treatment option is under review and will be described at the annual meeting. 

Adjuvant nivolumab (NIVO) plus ipilimumab (IPI) for resected high-risk stages IIIC/IV melanoma (MEL).  ASCO 2016. # 9586.  J Clin Oncol 34, 2016.  Khushalani, Kim, Gibney, et al.

Background: Patients (pts) with resected stage IIIC or IV melanoma are at very high-risk for recurrence and effective strategies for adjuvant therapy are needed. Combination NIVO + IPI yields high response rates but has a high rate of grades (G) 3-4 toxicities in advanced MEL. We examined the safety and efficacy of 2 dosing schedules of NIVO + IPI in resected stage IIIC and IV MEL pts. Methods: Resected stage IIIC/IV MEL pts who were free of disease, with adequate laboratory indices and performance status of 0-1 were treated with NIVO (1mg/kg) + IPI (3mg/kg) Q3 weeks X 4 doses (induction) followed by 2 years of NIVO at 3mg/kg Q2 weeks (Cohort A). Toxicities observed during induction led to opening of cohort B consisting of NIVO (3mg/kg) + IPI (1mg/kg) Q3 weeks X 4 doses followed by the same maintenance. Pre-defined criteria permitted initiation of NIVO maintenance following recovery from induction toxicity in both cohorts. Results: Twenty pts were treated in each cohort. Median age was 50 (22-78) in cohort A and 55 (29-77) in cohort B; stage IIIC pts constituted 65% and 60% of the respective cohorts. Toxicity precluded completion of all 4 induction doses in 50% in cohort A (most common was G3-4 ↑ AST and/or ALT in 7 pts) and 35% in cohort B. The most common G3-4 toxicities (minimum 5 events) are listed in the table. Hypophysitis developed in 28% (7 pts in cohort A). The incidence of ↑ AST/ALT, nausea, anorexia, cough, weight loss, neurotoxicity & endocrine toxicity was significantly higher in cohort A. In this group, 5 pts (25%) completed all induction doses and remain on NIVO maintenance; in group B, this number was 40%. There have been 4 relapses in cohort A, and 3 in cohort B. Only 1 pt in this high-risk study group has succumbed to MEL recurrence. At median follow-up of 21.3 months and 11 months respectively for the two cohorts, the median progression-free survival and overall survival have not been reached. Conclusions: In very high-risk resected MEL, adjuvant NIVO + IPI followed by maintenance NIVO has encouraging activity. Dosing per cohort B appears better tolerated and warrants further study. Clinical trial information: NCT01176474

	A (n = 20)	B (n = 20)
↑ Lipase	8	6
↑ ALT / AST	8 / 5	1 / 1
↑ Glucose	2	4
↑ Amylase	3	3
Colitis	3	2
Vomiting	1	4

Here's a post from 2015 that includes the reports from my study as well as one using ipi as adjuvant:  What to expect in Ipi vs Nivo Trial as adjuvant for resected melanoma???

Another post discussing BRAFi as adjuvant:   BRAFi as neoadjuvant

And here is a bit of an op-ed I wrote regarding adjuvant care with links within:  Adjuvant treatment in melanoma-limited options

Wishing my best to you all! - c