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
Way to go, ratties. Teaching the Big Dogs. And dogs...thanks for listening! - c
The key timeframe to evaluate response > = 3 months in this report - which is important!
ReplyDeleteAny 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!
If you look back on the Feb 23...time to response...slide from the ipi vs ipi/nivo trial...you 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!
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