Tumor response dynamics of advanced non-small-cell lung cancer (NSCLC) patients (pts) treated with commercial PD-1 inhibitors in the clinical setting.

Abstract

9087 Background: PD-1 inhibitors have shown promising activity in advanced NSCLC, with increasing clinical use. We evaluated tumor burden dynamics in advanced NSCLC pts treated with commercial PD-1 inhibitors to identify imaging markers for clinical benefit. Methods: The study included 160 advanced NSCLC pts (79 males; median age: 65) treated with commercial nivolumab or pembrolizumab monotherapy at DFCI as a part of routine clinical care. Tumor burden dynamics were assessed on serial CT scans during therapy by irRECIST1.1, which uses unidimensional measures and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. Results: Tumor burden change at best overall response (BOR) ranged from -100% to +278% (median: +3.5%). Objective response rate (ORR) was 18% (29/160). Current and former smokers had higher ORR than never smokers (ORR:14% (8/58), 25% (20/79), 4% (1/23); Fisher p = 0.04). Durable disease control with tumor burden < 20% increase from baseline for at least 6 months was noted in 27 pts (17%), which included 11 pts with stable disease as their irBOR. Using an 8-week landmark analysis, pts with < 20% tumor burden increase from baseline at 8 weeks had longer OS than pts with ≥20% increase (median OS:12.4 vs. 4.6 months, p < 0.001). In Cox models using a time varying covariate, pts with < 20% tumor burden increase during therapy had significantly reduced hazards of death (HR = 0.24, p < 0.0001) after adjusting for smoking (HR = 1.77, p = 0.016) and baseline tumor burden (HR = 1.66, p = 0.032). Two pts (1.3%) had atypical response pattern or “pseudoprogression”, where tumor burden showed initial increase and subsequent decrease, which was noted after confirmed irPD on consecutive scans in both pts. Conclusions: An objective response or durable disease control was noted in 25% of advanced NSCLC pts treated with PD-1 inhibitors in the clinical setting. Tumor burden increase of < 20% from the baseline during therapy was associated with longer OS, proposing a practical marker of clinical benefit. Pseudoprogression was uncommon, with tumor decrease noted after confirmed irPD, indicating a limitation of the current strategy for immune-related response evaluation.