96PD_PREvaluation 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

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 12.6 mo 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.Table96PD_PRPatients Receiving Therapy Post-PD per RECIST v1.1nmOS from time of first RECIST v1.1 PDAtezo arm pts continuing atezo6111.8 moAtezo arm pts receiving non-protocol anti-cancer therapy309.2 moDoc arm pts receiving non-protocol anti-cancer therapy469.7 mo Open table in a new tab Clinical trial identification: NCT01903993 Legal entity responsible for the study: F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group Funding: F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group Disclosure: A. Artal-Cortes: Advisory boards for Roche, BMS, MSD and travel fees from Roche. A. Rittmeyer: Grants as an advisor or speaker from Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. K. Park: Consulting/advisory from Astellas Pharma, AstraZeneca, BI, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche; speakers' bureau fees from BI; research funding from AstraZeneca. C. Lewanski: Consulting/Advisory: Roche, Celgene, Amgen. S. Liu: Employed by Genentech and holds Roche stocks. M. Ballinger: A Genentech employee and has Roche stock. All other authors have declared no conflicts of interest.