Tuesday, June 7, 2016

ASCO 2016 - Using amount of progression as marker of response and OS with anti-PD1

Immune-related tumor response dynamics as a marker for survival and treatment benefit during PD-1 inhibitor therapy.  ASCO 2016.  #9521.  J Clin Oncol 34, 2016.    Nishino, Giobbie-Hurder, Bailey, Hodi, et al.

PD-1 inhibitors are promising anti-cancer agents and are associated with unique immune-related response patterns. We characterized patterns of tumor response dynamics on CT scans during PD-1 inhibitor therapy and investigated the association with overall survival (OS) in advanced melanoma patients (pts). Methods: Forty-nine advanced melanoma pts (22 males; median age: 55) treated with single-agent pembrolizumab at DFCI were retrospectively studied. Baseline and all follow-up CT during therapy were reviewed to quantify tumor burden using irRECIST, which uses unidimensional measurements and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. Association between OS and tumor burden dynamics was studied. Results: Tumor burden change at best overall response ranged from -100% to 357% (median:-11%). Response rate was 41% . Spiderplot showed 3 distinct patterns of tumor response dynamics: A) tumor burden less than 20% increase from baseline throughout therapy (n = 27, 55%); B) tumor burden greater than/= to, 20% increase from baseline without subsequent response (n = 19, 39%); and C) pseudoprogression with initial tumor burden increase ( less than/= to, 20%) and subsequent response (n = 3, 6%). Pseudoprogressors were younger than others (median age: 40 vs. 56), and achieved response after irPD was confirmed on 2 consecutive scans. Using a 3-month landmark analysis, pts with less than 20% tumor burden increase from baseline at 3 months had longer OS than pts with greater than/=to 20% increase (12-month OS rate: 78 vs 51%). In extended Cox models, pts with < 20% tumor burden increase during therapy had significantly reduced hazards of death. Conclusions: Three distinct patterns of tumor response dynamics were noted during pembrolizumab therapy. Pseudoprogressors achieved response after experiencing confirmed irPD, indicating a limitation of the current strategy for immune-related response evaluation. Tumor burden less than 20% increase from baseline on follow-up CT scans was associated with longer OS, proposing a practical marker for survival and treatment benefit of PD-1 inhibitor therapy.

My take:
So....there are three patterns of response.  
1.  Tumor burden never increased more than 20% during treatment.
2.  Tumor burden that did increase, but no more than 20%, with no further improvement.
3.  Tumor burden that did increase, but no more than 20%, with subsequent improvement. (pseudoprogression...about 6% of patients) 

Early in treatment, within 3 months, if your tumor is essentially stable, or better, your overall survival is better.  If your tumor burden increases more than 20%....chances of response are unlikely.  Though there is the 5-6% of folks who demonstrate 'pseudoprogression' and later DO respond...however, this study points out that the amount of growth remains at a 20%, or less, increase.  Note:  This portion of responders with pseudoprogression at 5-6% is consistent with prior studies.

Clear as mud, right?  love, c

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