Early on-treatment tumor growth rate (EOT-TGR) determines treatment outcomes of advanced non-small-cell lung cancer patients treated with programmed cell death protein 1 axis inhibitor

Abstract

Background: Tumor growth rate (TGR), denoted as percentage change in tumor size per month, is a well-established indicator of tumor growth kinetics. The predictive value of early on-treatment TGR (EOT-TGR) for immunotherapy remains unclear. We sought to establish and validate the association of EOT-TGR with treatment outcomes in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) therapy.

Patients and methods: This bicenter retrospective cohort study included a training cohort, a contemporaneously treated internal validation cohort, and an external validation cohort. Computed tomography images were retrieved to calculate EOT-TGR, denoted as tumor burden change per month during a period between baseline and the first imaging evaluation after immunotherapy. Kaplan-Meier methodology and Cox regression analysis were conducted for survival analyses.

Results: In the pooled cohort (n = 172), 125 patients (72.7%) were males; median age at diagnosis was 58 (range 28-79) years. Based on the training cohort, we determined the optimal cut-off value for EOT-TGR as 10.4%/month. Higher EOT-TGR was significantly associated with inferior overall survival [OS; hazard ratio (HR) 2.93, 95% confidence interval (CI) 1.47-5.83; P = 0.002], worse progression-free survival (PFS; HR 2.44, 95% CI 1.46-4.08; P = 0.001), and lower objective response rate (3.3% versus 20.9%; P = 0.040) and durable clinical benefit rate (6.7% versus 41.9%; P = 0.001). Results were reproducible in the two validation cohorts for OS and PFS. Among 43 patients who had a best response of progressive disease in the training cohort, those with high EOT-TGR had worse OS (HR 2.64; P = 0.041) and were more likely to progress due to target lesions at the first tumor evaluation (85.2% versus 0.0%; P <0.001).

Conclusions: Higher EOT-TGR was associated with inferior OS and immunotherapeutic response in patients with aNSCLC undergoing anti-PD-1/PD-L1 therapy. This easy-to-calculate radiologic biomarker may help evaluate the abilities of immunotherapy to prolong survival and assist in tailoring patients' management.

Trial registration: ClinicalTrials.govNCT04722406; https://clinicaltrials.gov/ct2/show/NCT04722406.

Keywords: biomarker; immunotherapy; non-small-cell lung cancer; prognosis; tumor growth rate.