Characterization of patients treated with a programmed cell death protein 1 inhibitor (anti-PD-1) past RECIST progression from a metastatic non-small cell lung cancer (mNSCLC) trial.

Abstract

3000 Background: Anti-PD-1 monoclonal antibodies are immunotherapy agents that block T cell inhibitory signal pathways. Anecdotal cases have been reported of clinically important decrease in tumor size following initial evidence of RECIST-defined disease progression. We describe the findings in patients with treatment past RECIST-defined progression (TPP) observed in a trial of mNSCLC patients receiving an anti-PD-1. Methods: Data from a trial evaluating an anti-PD-1 for the treatment of patients with mNSCLC who progressed after platinum- doublet chemotherapy, demonstrating a clinical benefit for an anti-PD-1, was evaluated. Per protocol, patients were allowed to receive TPP if they were not experiencing rapid disease progression, had stable performance status, and written informed consent was obtained. We identified anti-PD-1-treated patients with TPP in this study and evaluated the changes in tumor burden following RECIST-defined progression in these patients. Results: In total, 71 patients received TPP with an anti-PD-1 and their best overall responses by RECIST v1.1 were progressive disease in 35 (49%), stable disease in 23 (32%), and partial response (PR) in 13 (18%); the PR rate was similar in patients with and without TPP. Among patients with TPP, RECIST-defined progression was based on an increase in the sum of longest diameter (SLD) of target lesions (TLs) in 37 (52%) patients, the appearance of new lesions (NLs) in 33 (46%), and/or unequivocal progression of non-target lesions (NTLs) in 28 (39%) patients. Among the TPP patients, 4 patients (5.6%) experienced additional tumor shrinkage. One patient with RECIST-defined progression based on ≥ 20% increase in SLD of TLs and three patients based on NLs or unequivocal progression of NTLs demonstrated a subsequent ≥ 30% decrease in SLD as compared to nadir. Conclusions: Our evaluation suggests that anti-PD-1-treated patients with mNSCLC generally do not benefit from TPP. The risks of continued treatment should be considered in light of the low likelihood of tumor shrinkage with TPP with an anti-PD-1 agent.