Taichi Miyawaki1, Hirotsugu Kenmotsu2, Keita Mori3, Eriko Miyawaki4, Nobuaki Mamesaya4, Takahisa Kawamura4, Haruki Kobayashi4, Shota Omori4, Kazushige Wakuda4, Akira Ono4, Tateaki Naito4, Haruyasu Murakami4, Hideyuki Harada5, Masahiro Endo6, Yasuhisa Ohde7, Kazuhisa Takahashi8, Toshiaki Takahashi4. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan; Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan. Electronic address: h.kenmotsu@scchr.jp. 3. Division of Clinical Research Promotion Unit, Shizuoka Cancer Center, Nagaizumi, Japan. 4. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan. 5. Radiation and Proton Therapy Center, Shizuoka Cancer Center, Nagaizumi, Japan. 6. Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi, Japan. 7. Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi, Japan. 8. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC. PATIENTS AND METHODS: The present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions' longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs). RESULTS: The optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS. CONCLUSIONS: PD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.
BACKGROUND: Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC. PATIENTS AND METHODS: The present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions' longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs). RESULTS: The optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1tumor proportion score of ≥ 50% were independently associated with prolonged PFS. CONCLUSIONS:PD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.
Keywords:
Baseline number of metastatic lesions; Baseline sum of target lesions’ longest diameters; Clinical biomarker; Programmed cell death 1 inhibitors; Programmed cell death ligand 1 inhibitors