Pseudoprogression in cancer immunotherapy: Rates, time course and patient outcomes.

6580 Background: Pseudoprogression (PP), tumor growth from treatment effect rather than true disease progression, has been described with immune checkpoint inhibitors. Our study measures rates and time course of PP and associated patient outcomes using RECIST 1.1 and irRC criteria. Methods: Cohort was retrospectively drawn from subjects enrolled in phase I and II trials from March 2008 to July 2015 at two hospitals within one cancer center network. Inclusion required followup with every 4-12 week scheduled torso CT or MRI for > 1 year or until death analyzed using RECIST 1.1 and irRC criteria by the imaging core lab. A single investigator blinded to patient outcome abstracted the core lab database; another blinded to imaging assessment abstracted patient survival from the medical record. Pattern of response during the first year of therapy assessed according to RECIST 1.1 and irRC criteria were categorized as stable (SD), partial response (PR), progressive disease (PD) or pseudoprogression (PP). PP was defined as progression from nadir followed by response from peak. Results: Cohort of 356 was comprised of 214 melanoma, 103 non-small and 6 small cell lung, 16 breast, and 17 other cancer patients. Therapeutic agents were anti-PD1 (203, 57%), anti-PD-L1 (82, 23%), CTLA-4 alone (57, 16%) or in combination with anti-VEGF (5, 1%) or BRAF(V600E) inhibitor (4, 1%). 193 (54%) were alive at 1 year. Number (% of cohort) classified as SD, PR, PD and PP respectively was 59 (17%), 98 (28%), 192 (54%) and 7 (2%) with RECIST and 66 (19%), 101 (28%), 168 (47%) and 21 (6%) with irRC. PP rates between the two criteria were different (p < 0.01). Number (% in category, 95% CI) alive at 1 year respectively was 38 (64%, 51-75), 81 (84%, 74-89), 67 (35%, 29-42) and 7 (100%, 65-100) with RECIST and 38 (58%, 46-69), 82 (82%, 72-88), 56 (33%, 27-41) and 17 (81%, 60-92) with irRC. In the PP group, mean days (range) from baseline to progression, to response and intervening time in between were 74 (29-108), 169 (57-277), and 94 (28-169) with RECIST and 88 (29-181), 187 (57-364) and 99 (28-276) days with irRC. Conclusions: Pseudoprogression is uncommon and indicates a high likelihood of > 1 year survival. Complete course of progression from nadir followed by response from peak can take up to 1 year.