Durable responses to pembro. The 'C' word (CURE!!!!!!!!!!) used by melanoma researchers. And....HAPPY NEW YEAR!!!!

This is how to leave 2017 with a bang!!!!! We know that among melanoma patients there is a roughly 15% response rate to ipi and about a 40% response rate to anti-PD-1.  But, if you are a responder...how long will the response last?  I've been talking about "durable benefit" and melanoma treatments for years.  Being disease free for 10 minutes doesn't mean that much, now does it?  Here are some previous posts on durable responses ~
2016:  Nivolumab Shows Impressive OS in melanoma
2015:  Ipi for melanoma...the data keeps pouring in...and it's pretty good!
2014:  Review of immunotherapy and durable benefit in melanoma!!!

The authors in the 2016 Nivo paper above looked at overall and progression free survival and note: 

“These data represent the longest survival follow-up of patients who received anti–PD-1 therapy in a clinical study, and suggest durable, long-term survival with nivolumab monotherapy,” said lead investigator F. Stephen Hodi,

“In all patients, there is a plateauing, a so called tail on the curve, and it’s lasting many months to years, and about a third of patients have this long-term survival,” said Hodi. “Those who make it to 48 months, have a very good chance of surviving their disease.”

“What distinguishes immunotherapy from other forms of cancer treatment is the durability of the benefit. Those who have complete responses seem to be protected from that disease recurring,” said Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center, who moderated a press conference. “The memory and the adaptability of the immune response to pick off resistant variables is an important take-home here. These are very compelling data to suggest that this is the case.”

This article looks at the staying power of COMPLETE responses...a bit different from "response rate" which includes those with complete and partial responses...

Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. Robert, Ribas, Hamid, Daud, Wolchok...Weber...Hodi. J Clin Oncol. 2017 Dec 28.  

Purpose: Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827).

Patients and Methods: Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for greater than/= to 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses.

Results:  Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of greater than/ = to 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis.

Conclusion: Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

Basically, this report looks at folks treated with pembro who had a complete response (CR). A complete response was noted in 105 (of 655) patients treated, which turned out to be 16%.  There are a few other details, but ultimately of the 105 patients with a complete response, their disease free survival rate at 2 years was 91%.  67 of those 105 patients with a complete response opted to discontinue pembro (and have no further treatment - only observation) after they attained their complete response, and 90% of them remained disease free at 2 years.  In other words, there was little difference between the complete responders' 2 year survival, no matter if they continued their treatment beyond their CR or not.

While this durability, combined with the promise of nivo as adjuvant for Stage III and IV NED patients, as well as BRAF/MEK, nivo, pembro, and the ipi/nivo combo for folks with advanced melanoma is an excellent note on which to end 2017 ~ I am looking forward to a 2018 filled with improvements in melanoma care that include more responses overall and an even greater number of complete responses!!!

Bless you one and all!  Cheers! - love, c