267 Pseudoprogression patterns: Analysis from 2 independent phase-2 studies with immunotherapy for recurrent cervical cancer

BackgroundThe phenomenon of pseudoprogression (PsP) may appear with cancer immunotherapy. The underlying etiology is not fully elucidated, tumor flare is the suspected mechanism of early pseudoprogression that may resolve gradually while continuing treatment. Further, immunotherapy-induced sarcoidosis may mimic PsP. Here we present examples of 3 observed patterns of PsP in cervical cancer (CC) patients treated with balstilimab (BAL; anti-PD-1), alone or in combination with zalifrelimab (ZAL; anti-CTLA-4).MethodsThe evaluated patients received either BAL 3 mg/kg every 2 weeks alone (NCT03104699) or in combination with ZAL dosed at 1 mg/kg every 6 weeks (NCT03495882). PsP was defined as radiologic disease progression per RECIST1.1 followed by a significant reduction of measurable baseline lesions, disappearance of the non-measurable lesions, or no further progression for at least two tumor assessments after initial progressive disease (PD) by Independent Evaluation Review Committee (IERC). PsP was divided into 3 categories – early (before or at week 12 of treatment), delayed (after week 12) and serial (at least 2 PsP occurrences).ResultsOverall, 313 patients with post-chemotherapy recurrent CC with baseline measureable disease were treated with either BAL (n=160) or in combination with ZAL (n=143). Early PsP was observed in 7 patients treated with BAL and 8 with BAL/ZAL while 5 patients experienced delayed PsP (BAL (n=1); ZAL(n=4)). Serial PsP was observed in 1 patient (BAL only) and another (n=1) BAL treated experienced showed PsP (new Mediastinal lesions) present in 2 consecutive CT scan evaluations before disappearance – hence were classified as PD even by iRECIST. Immune-related sarcoidosis was confirmed histologically in 2 patients following confirmation by mediastinal lymph node biopsy. PsPs were accompanied with clear clinical benefit of disease improvement and weight stabilization, improvement in performance status, and decreased painPsP BAL (N=160)) BAL/ZAL (N=143)Early 7 (4%) 8 (6%)Delayed 1 (