NEW ipi vs nivo trial for resected melanoma patients!!!!!!!!!!!!!!!!!!!!!!!!

With all the advancements (ie new drugs) that have occurred over the past 4 years in the treatment of melanoma, several large HICCUPS remain for many, many patients.

But first....a quick review:

Ipi (Ipilimumab or Yervoy) - a CTLA-4 checkpoint inhibitor (immunotherapy).  FDA approved for patients with Stage IV metastatic melanoma.  Response rate = 15-20% for those patients.

BRAF inhibitors (Dabrafenib [Tafinlar] and Vemurafenib [Zelboraf]) - work only in patients with the BRAF mutation. FDA approved for metastatic melanoma. Response rate = 50-80% (depending on the group and study you look at - most researchers have now agreed upon 70% as the response rate).  Big problem with these drugs, apart from their effectiveness being limited to patients with the mutation, is that the duration of their effectiveness has been documented to be only 3-7 months.  However, with the addition of MEK inhibitors (Trametinib, Cobimetinib, Binimetinib, Selumetinib, and a few others) taken simultaneously, duration of effect has been lengthened and side effects have been diminished.

Anti-PD1 drugs (Nivolumab [Opdivo] and Pembrolizumab [Keytruda]) - Both are FDA approved for patients with Stage IV metastatic melanoma AFTER having failed ipi and BRAFi (if BRAF positive).  Have about a 40% response rate.

Have you guessed the HICCUPS yet?  Well, the first and most obvious one....is that the two drugs with the BEST RESPONSE RATES, given duration of effect and side effect profile, are FDA approved (read:  that's how insurance will pay for them!!!) only AFTER patients have failed to respond to ipi and BRAFi.  I could go on and on about that...but here is the other HICCUP....

I have had melanoma skin lesions, brain mets, a lung met and a tonsilar met.  I was also lucky enough to participate in a nivo trial for resected patients in 2010, took the drug for 2 1/2 years...and have been NED ever since.  BUT!!!  WHAT if?  What if I get a met, that I would be lucky enough to have surgically removed (because that....after all...is still what helps patients survive melanoma the most!!!)?  What treatment would I, a Stage IV melanoma patient with multiple recurrences, have access to after I removed the new met?  ONLY ONE!!!!!!!!!!!!

Interferon!! An ancient immunotherapy that was offered to me when I was first diagnosed.  It makes patients so sick that few are able to complete the year that is recommended and has a response rate of MAYBE 10% with very little impact on overall survival.

STILL!!!!   After all this time.  After all the ratties who like me....are doing well after resection and ANY of the drugs listed above.  After study after study has PROVEN that all of these drugs work best when the patient has the lowest disease burden possible.  That's it.  If you have Stage III/IV melanoma and have surgery to remove your tumor....the only option you have for treatment without being in a trial...is interferon.  (Even IL2 is not used in an adjuvant setting....and I'm not sure it should be since it is such a tough therapy that 2-3% of patients can die from the drug alone and that risk may not be a wise balance when you are resected.)

So...if you have resected melanoma with a high risk of recurrence here are your options:

Adjuvant trials currently being offered include -Vitamin supplements, various vaccines, quality of life and family hx with observation measurements, nifty tests to ID tumor markers, radiation, electroporated autologous dendritic cells, IL 2 vs Dacarbazine, Ipi vs high dose interferon, Tamimogene Lakerparevec and surgery vs surgery alone, Vemurafenib vs placebo, Dabrafenib with trametinib, and though not yet recruiting - Pembrolizumab vs placebo.

That's it.  Those are the trial options for resected patients.  The drugs with the most effect are often placed up against placebo.  But....there is a new trial option just starting....

IPI vs NIVO for Stage IIIb/c or Stage IV melanoma after complete resection

Dr. Weber spoke to us about it on our last visit, but it has only just been posted to the ClinicalTrials.gov site.  It is not yet recruiting, but will be soon.  I don't know of locations other than Tampa yet.  Complete resection is required.  No previous cancer treatments are allowed.  Patients with ocular and uveal melanoma are excluded.

So...there's the info.  It is certainly a trial I would have signed up for had it been available in 2010. I hope it helps many.  Here's to the ratties....who someday will convince the powers that be, that folks with resected melanoma need better REAL treatment options!!!  - c