The value of blinded independent central review (BICR) in recent trials in non-small cell lung cancer (NSCLC).

e23000 Background: Progression free survival (PFS) is an endpoint that has been increasingly used to obtain approval of new cancer drugs and strategies. However, there are a number of issues that can complicate assessment of PFS. One of these is the potential for investigator bias. This has been addressed by the use of blinded independent central review (BICR). However, BICR increases costs and complexity. Methods: The current study evaluated the results of BICR versus investigator assessment (IA) for phase III randomized clinical trials in thoracic oncology with initial publication from 1.01.2013-12.31.2023. Trials were included if they involved targeted agents, antibody drug conjugates or immunotherapy. Studies with < 100 pts or comparing only cytotoxic chemotherapy or maintenance strategies were excluded. Studies with cytotoxic chemotherapy as part of therapy or within the control arm were included. A search of clinicaltrials.gov with the terms “phase III”, “non-small cell lung cancer” for completed studies was done, supplemented by a bibliographic search. Publications were then reviewed for whether a BICR was utilized and whether both BICR and IA were reported. Hazard Ratios (HR) for PFS between IA vs BICR were compared. Results: 49 randomized phase III trials were identified of which 34 describe BICR of which 21 reported both IA and BICR results. Six studies evaluated immunotherapy and enrolled 3337 pts, 15 evaluated targeted agents and enrolled 6531 pts. All immunotherapy studies were significantly positive for the experimental arm and 14 of 15 of the targeted therapies were positive. PFS data was reported for 17 of the studies (not reached for experimental arms in 2 and not reported in 2 others). HRs were directionally similar in all studies, though were lower (more favorable) in IA vs BICR in 5 of 6 immunotherapy studies and 11 of 15 targeted therapy studies. The mean % difference for immunotherapy studies was 8.9% and the median 10%, range 2-23.5%. For the positive targeted therapies studies the mean/median differences were 14.6%/15.6%, range 1.5-42%. The largest % differences were seen at the lowest HRs (e.g..19 vs .27; 42%). For immunotherapy studies, the median PFS difference was 0.2 and 0.28 months for the control and experimental arms, respectively. For targeted therapy studies, median PFS differences were 0.4 and 0.95 months for the control and experimental arms, respectively. The studies were performed in multiple countries including the United States, European Union, China and Japan. Conclusions: Despite a wide range of agents and settings, no trial for which information is publicly available comparing BICR to IA has demonstrated any qualitative difference in outcome nor more than a marginal numerical difference.