Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study

Toshiki Ogiwara; Hitoshi Kawazoe; Saeka Egami; Hironobu Hashimoto; Yoshimasa Saito; Naomi Sakiyama; Yuichiro Ohe; Masakazu Yamaguchi; Tetsuya Furukawa; Azusa Hara; Yui Hiraga; Aya Jibiki; Yuta Yokoyama; Sayo Suzuki; Tomonori Nakamura

doi:10.3389/fonc.2021.770268

Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study

Front Oncol. 2021 Nov 8:11:770268. doi: 10.3389/fonc.2021.770268. eCollection 2021.

Authors

Toshiki Ogiwara¹, Hitoshi Kawazoe^{1

2}, Saeka Egami¹, Hironobu Hashimoto³, Yoshimasa Saito³, Naomi Sakiyama³, Yuichiro Ohe⁴, Masakazu Yamaguchi⁵, Tetsuya Furukawa³, Azusa Hara⁶, Yui Hiraga¹, Aya Jibiki¹, Yuta Yokoyama^{1

2}, Sayo Suzuki^{1

2}, Tomonori Nakamura^{1

2}

Affiliations

¹ Division of Pharmaceutical Care Sciences, Center for Social Pharmacy and Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, Tokyo, Japan.
² Division of Pharmaceutical Care Sciences, Keio University Graduate School of Pharmaceutical Sciences, Tokyo, Japan.
³ Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan.
⁴ Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁶ Division of Drug Development and Regulatory Science, Keio University Faculty of Pharmacy, Tokyo, Japan.

Abstract

Background: Nivolumab and pembrolizumab are the standard treatments for patients with advanced non-small-cell lung cancer (NSCLC). While there are reports on several inflammatory indices and the prognosis of patients with cancer, no study has combined baseline medication with the neutrophil-to-lymphocyte ratio (NLR) to predict clinical outcomes. This study investigated the efficacy of baseline medications plus NLR to predict the effectiveness of nivolumab and pembrolizumab in a real-world clinical setting.

Methods: We conducted a single-center retrospective observational study of consecutive patients with advanced NSCLC who received nivolumab or pembrolizumab as first-line, second-line, or beyond treatment between December 2015 and November 2018 at the National Cancer Center Hospital in Japan. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The drug-based prognostic score for baseline medications plus NLR was weighed based on the regression β coefficients. The multivariable Cox proportional hazard model was used to assess the association between the prognostic score-stratified groups and survival outcomes.

Results: In total, 259 patients were evaluated in this study. A prognostic score calculated from the baseline medications plus NLR was used to categorize the patients into good (score 0), intermediate (scores 1-2), and poor (scores 3-6) -prognosis groups. The multivariable Cox proportional hazard model revealed a significant association between the poor-prognosis group and reduced OS. The hazard ratio of OS was 1.75 (95% confidence interval: 1.07-2.99; P = 0.031). In contrast, no association between these prognosis groups and PFS was observed.

Conclusions: The findings suggest that the baseline medications with nivolumab or pembrolizumab plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC and could be used as a prognostic index for poor outcomes. However, to ascertain the clinical application of these findings, these concomitant medications need further validation in a large-scale multicenter study.

Keywords: baseline medications; neutrophil-to-lymphocyte ratio; nivolumab; pembrolizumab; prognostic score.