Prolonged survival in Stage III melanoma treated with ipi as adjuvant!!!

Having developed brain and lung mets in 2010, I was unceremoniously thrust from my 2003 Stage 3b melanoma diagnosis to Stage IV!  I got busy ~ zapping the brain met and removing the upper lobe of my lung to rid myself of the melanoma there.  Then...nothing.  There were no FDA approved drugs for melanoma available (other than interferon...so, yeah.  Nothing.).  No BRAFi, ipi, much less anti-PD1.  Trials were practically nonexistent, because, as I quickly discovered, almost all of them required "measurable disease", something I had just gone to a great deal of trouble to rid myself of!!!!  Through perseverance, almost endless computer searches and phone calls bordering on the level of insanity, B did find one trial for which I qualified - the NED arm of a Phase 1 Nivo/vaccine trial at Moffit.  (This was back when Nivolumab, now Opdivo, was known as MDX1106 and I was certain melanoma was going to kill me!!)  Despite how well I and my fellow ratties have done for the most part (blessings and sorrow for those who did not fare as well) adjuvant treatments for melanoma patients are still hard to find.  It should not be this way!!!  

Here is one recent post addressing "progress" for NED melanoma patients as well as a link to the results of my NED/nivo study:  Surgical management and adjuvant therapy for high risk melanoma - still waiting for answers!!

The only FDA approved treatments for NED patients currently, are interferon (Crazy, right????) and ipi. Now there is this report:

Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy.  Eggermont, Chiarion-Sileni, Grob, Dummer, Wolchok, Schmidt, Hamid, Robert, Ascierto, Richards, Lebbé, Ferraresi, Smylie, Weber, ... , Hodi , et al.  N Engl J Med. 2016 Oct 7. 

On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group. The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group. The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group. Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.  As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. 

Not surprisingly, Stage III, NED folks treated with ipi did much better than those without treatment in recurrence-free survival, overall survival, and in their rate of distant metastasis.  Also, not surprisingly, they developed more side effects from ipi than did the folks who did not get it!!!  All of this is good news. (Well...not the side effects!!!)  Hopefully, the folks who responded will remain melanoma free forever.  BUT! This is not enough.  Anti-PD1 remains off limits for these same patients....even though we KNOW that these drugs have a better response rate, fewer side effects, AND when taken BEFORE ipi - a much higher response rate than when taken after!!!  Check out this link - to the tune of... Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! FDA! Are you listening??????? 

While I am thrilled that Stage III/IV NED melanoma patients DO have ipi available to them and that this report confirms its value ~ and while I would have jumped at the chance to take ipi back in 2010 ~ we can do better.  These folks deserve better.  And no, I will not stop saying it!!!!! - c