Evaluation of non-classical response by immune-modified RECIST and efficacy of atezolizumab beyond disease progression in advanced NSCLC: Results from the randomized Phase II study POPLAR

Abstract

Background: Response patterns following cancer immunotherapy (CIT) treatment are often non-classical due to tumor immune infiltration and increase in tumor burden prior to response. As such, RECIST-based endpoints may not adequately predict the potential OS benefit with CIT. In an updated analysis of POPLAR, PFS and ORR improvement with atezolizumab (atezo) vs docetaxel (doc) was restricted to patients (pts) with high PD-L1 expression, whereas OS benefit was seen in the PD-L1-unselected ITT population (HR, 0.69; mOS 12.6mo vs 9.7 mo with atezo vs doc), suggesting that many pts derive atezo benefit after radiographic progression. Methods: 287 NSCLC (2L/3L) pts were randomized 1:1 to receive atezo (1200 mg IV q3w) until loss of clinical benefit or doc (75 mg/m2 IV q3w) until PD per RECIST v1.1 (RECIST). The primary endpoint was OS; secondary endpoints included PFS and ORR per RECIST. Atezo arm pts were evaluated per immune-modified RECIST (imRECIST) and post-PD radiographic changes. Both arms were evaluated for OS post-PD (data cutoff, Dec 1, 2015; minimum follow-up, 20 mo). Results: Among 144 pts in the atezo arm, ORR per imRECIST vs RECIST was 17% vs 15%, disease control rate (CR+PR+SD) was 65% (imRECIST) vs 52% (RECIST) and mPFS was 4.3 mo (imRECIST) vs 2.7 mo (RECIST). In 61 atezo pts continuing treatment post-PD, 8% had a subsequent 30% decrease in target lesions relative to the time of PD, and 74% had a best change between +20% and 30%. mOS post-PD in both arms is shown (Table). Conclusions: Increased ORR and PFS per imRECIST vs RECIST in atezo pts highlight the utility of imRECIST as response evaluation criteria to assess efficacy of atezo/CIT. 82% of pts continuing atezo post-PD had subsequent stable (-+20% change) or decreased target lesions. The nearly 1-yr mOS in pts continuing atezo vs other treatment post-PD is suggestive of atezo benefit lasting beyond PD. Table.