Ipi/Nivo combo 5 year overall survival report for peeps with advanced melanoma!

As a convenient follow-up to my September report Melanoma patients want to know! What do I choose? Targeted or immunotherapy? What happens then? in which I addressed the latest survival data for both targeted and immunotherapy, a report coming from some Melanoma Big Dogs on the 5 year OS of the ipi/nivo combo was just released. 

This ASCO 2019 report, linked my previous post noted:  Long-term follow-up of CA209-004: A phase I dose-escalation study of combined nivolumab (NIVO) and ipilimumab (IPI) in patients with advanced melanoma.  2019 ASCO.  Akins, Kirkwood, Wolchok, ..., Postow, ...Sznol.  J Clin Oncol 37, 2019. 

"Results: At a median follow-up of 43.1 months in all cohorts (N = 94), the 4- and 4.5-year OS rates were both 57%. The 4-year OS rates for pts with normal (n = 58) versus elevated LDH (n = 36) were 62% versus 49%; for pts with wild-type (n = 66) and mutant (n = 24) BRAF tumors, 4-year OS rates were 54% and 61%, respectively. Following the last dose of study drug (for any reason), overall post-treatment 1-, 2-, and 3-year OS rates were 74%, 65%, and 56%, respectively; in pts who discontinued due to study drug toxicity (n = 32), post-treatment 1-, 2-, and 3-year OS rates were 84%, 75%, and 65%, respectively, and in pts who discontinued for disease progression (n = 30), these were 52%, 34%, and 24%, respectively. Conclusions: This updated analysis from study CA209-004 showed favorable survival outcomes with NIVO+IPI, regardless of BRAF or LDH status, and provided evidence of long-term survival following discontinuation of treatment in pts with advanced melanoma. "

Now, there's this ~

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.  Larkin, ..., Lebbe, ..., Ascierto, ...Long, ...Hodi, Wolchok.  N Engl J Med. 2019 Sep 28. 

Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.

At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group. Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.

Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab.

So - the ASCO report broke various factors down a bit, but generally noted:  "overall post-treatment 1-, 2-, and 3-year OS rates were 74%, 65%, and 56%, respectively".  In this new report the OS at 5 years for the ipi/nivo combo = 52%, for nivo alone = 44%, and ipi alone = 26%.  Given what we have been seeing in the research these numbers are pretty consistent with expectations.  The ipi/nivo combo peeps didn't quite hold onto the 3 year survival number of 56%, the data point where those who are fond of kaplan meier curves note things flatten out, but it is pretty close.  I do want to reiterate from the ASCO report, "pts who discontinued due to study drug toxicity (n = 32), post-treatment 1-, 2-, and 3-year OS rates were 84%, 75%, and 65%, respectively.   I think it is reasonable to assume that while the 5 year OS in that group may well decrease a bit, that would still be a good number! (Considering we are talking melanoma world y'all!!!)  

Pretty hopeful stuff when you consider that in 2010, NONE of the current therapies attaining these survival results for melanoma patients were FDA approved.  Not even ipi.  NOW!  Let's get some help for that other 50% of our melanoma peeps!!! - c