Pre-Treatment Tumor Growth Rate Predicts Clinical Outcomes of Patients With Advanced Non-Small Cell Lung Cancer Undergoing Anti-PD-1/PD-L1 Therapy
Lina He, Xuanye Zhang, Haifeng Li, Tao Chen, Chen Chen, Yixin Zhou, Zuan Lin, Wei Du, Wenfeng Fang, Yunpeng Yang, Yan Huang, Hongyun Zhao, Shaodong Hong, Li Zhang
Abstract
Tumor growth rate (TGR; percent size change per month [%/m]) is postulated as an early radio-graphic predictor of response to anti-cancer treatment to overcome limitations of RECIST. We aimed to evaluate the predictive value of pre-treatment TGR (TGR 0 ) for outcomes of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1/PD-L1 monotherapy. We retrospectively screened all aNSCLC patients who received PD-1 axis inhibitors in Sun Yat-Sen University Cancer Center between August 2016 and June 2018. TGR 0 was calculated as the percentage change in tumor size per month (%/m) derived from two computed tomography (CT) scans during a “wash-out” period before the initiation of PD-1 axis inhibition. Final follow-up date was August 28, 2019. The X-tile program was used to identify the cut-off value of TGR 0 based on maximum progression-free survival (PFS) stratification. Patients were divided into two groups per the selected TGR 0 cut-off. The primary outcome was the difference of PFS between the two groups. The Kaplan-Meier methods and Cox regression models were performed for survival analysis. A total of 80 eligible patients were included (54 [67.5%] male; median [range] age, 55 [30-74] years). Median (range) TGR 0 was 21.1 (-33.7-246.0)%/m. The optimal cut-off value of TGR 0 was 25.3%/m. Patients with high TGR 0 had shorter median PFS (1.8 months; 95% CI, 1.6 - 2.1 months) than those with low TGR 0 (2.7 months; 95% CI, 0.5 - 4.9 months) ( P = 0.005). Multivariate Cox regression analysis revealed that higher TGR 0 independently predicted inferior PFS (hazard ratio [HR] 1.97; 95% CI, 1.08-3.60; P = 0.026). Higher TGR 0 was also significantly associated with less durable clinical benefit rate (34.8% vs. 8.8%, P = 0.007). High pre-treatment TGR was a reliable predictor of inferior PFS and clinical benefit in aNSCLC patients undergoing anti-PD-1/PD-L1 monotherapy. The findings highlight the role of TGR 0 as an early biomarker to predict benefit from immunotherapy and could allow tailoring patient’s follow-up.