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Background: PD-1 inhibitors are promising anti-cancer agents and are associated ith unique immune-related response patterns. We characterized patterns of tumor response dynamics on CT scans during PD-1 inhibitor therapy and investigated the association ith overall survival OS in advanced melanoma patients pts . Methods: Forty-nine advanced melanoma pts 22 males; median age: 55 treated ith single-agent pembrolizumab at DFCI ere retrospectively studied. Baseline and all follo-up CT during therapy ere revieed to quantify tumor burden using irRECIST, hich uses unidimensional measurements and includes ne lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. Association beteen OS and tumor burden dynamics as studied. Results: Tumor burden change at best overall response ranged from -100 percent to 357 percent median:-11 percent . Response rate as 41 percent 2049; irCR in 4, irPR in 16 . Spiderplot shoed 3 distinct patterns of tumor response dynamics: A tumor burden lt 20 percent increase from baseline throughout therapy n = 27, 55 percent ; B tumor burden 20 percent increase from baseline ithout subsequent response n = 19, 39 percent ; and C pseudoprogression ith initial tumor burden increase 20 percent and subsequent response n = 3, 6 percent . Pseudoprogressors ere younger than others median age: 40 vs. 56; p = 0.05 , and achieved response after irPD as confirmed on 2 consecutive scans. Using a 3-month landmark analysis, pts ith lt 20 percent tumor burden increase from baseline at 3 months had longer OS than pts ith 20 percent increase 12-month OS rate: 78 vs 51 percent . In extended Cox models, pts ith lt 20 percent tumor burden increase during therapy had significantly reduced hazards of death HR = 0.16, 95 percent CI 0.05 - 0.54 , p = 0.003 univariate; HR = 0.14, 95 percent CI 0.04 - 0.48 , p = 0.002 multivariable . Conclusions: Three distinct patterns of tumor response dynamics ere 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 lt 20 percent increase from baseline on follo-up CT scans as associated ith longer OS, proposing a practical marker for survival and treatment benefit of PD-1 inhibitor therapy.,J Clin Oncol 34, 2016 suppl; abstr 9521 00:00.0,MelanomaSkin Cancers
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