Akihiro Tamiya1, Motohiro Tamiya2, Hirofumi Go3, Takako Inoue4, Kei Kunimasa4, Kenji Nakahama5, Yoshihiko Taniguchi1, Takayuki Shiroyama6, Shun-Ichi Isa7, Kazumi Nishino4, Toru Kumagai4, Hidekazu Suzuki8, Tomonori Hirashima8, Shinji Atagi7, Ayumi Shintani3, Fumio Imamura4. 1. Internal Medicine, Kinki-Chuo Chest Medical Center, Osaka, Japan. 2. Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan moto19781205@yahoo.co.jp. 3. Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 5. Respiratory Medicine, Ishikiriseiki Hospital, Osaka, Japan. 6. Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan. 7. Clinical Research Center, Kinki-Chuo Chest Medical Center, Osaka, Japan. 8. Thoracic Malignancy, Osaka Habikino Medical Center, Osaka, Japan.
Abstract
AIM: Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. PATIENTS AND METHODS: Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. RESULTS: The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. CONCLUSION: The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC. Copyright
AIM: Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. PATIENTS AND METHODS: Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. RESULTS: The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. CONCLUSION: The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC. Copyright