Monday, March 21, 2016

Melanoma big dogs review results of pts treated with Pembro = Don't stop too soon!!!

I've posted it a zillion times from all sorts of articles and webinars ~ when dealing with immunotherapy... 'Be patient with the patient!'...(from the webinar by Weber and Agarwala).  Repeatedly we've been warned that "progression" and "pseudoprogression" early on has to be evaluated with a grain of salt...rather than considering the measure ineffective and  yanking patients off their therapy as one fellow rattie was in my Nivo trial back in 2010 before we learned better.  (Though, if you've forgotten....while Weber was looking for another treatment for him...he started to improve!!!!  And continued to do so....with no further treatment.)  Folks treated with various immunotherapies, and combo's of same, have had side effects that rendered continuation of such treatment impossible.  Yet....they continued to respond.  Here a cadre of melanoma big dogs look at the results of 655 patients treated with pembro and tell us that as many as 15% of those treated could have had their treatment effect disregarded if old time evaluative criteria continue to be utilized.....

Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab.  Hodi, Weber, Daud, Hamid, Patnaik, Ribas, Wolchok, et al.  J Clin Oncol. 2016 Mar 7.

"We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study.

Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with greater than/= 28 weeks of imaging. Pseudoprogression was defined as greater than/= 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Of the 655 patients with melanoma enrolled, 327 had greater than/= 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived greater than/= 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177).

Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment."

Way to go, ratties.  Teaching the Big Dogs.  And dogs...thanks for listening! - c


  1. The key timeframe to evaluate response > = 3 months in this report - which is important!

    Any tumor assessment earlier than this may be misleading ( unless it's significant progression - both clinical and radiologic) . Some trials / clinicians would stop / change at the 2 month mark and in such a scenario the % of pseudo progression may be higher!

  2. If you look back on the Feb 23...time to response...slide from the ipi vs ipi/nivo will see outliers who fail to respond for 6 - 10 months out! Old news now....really. We all owe the ratties....who taught us that!