Nivolumab in Non-Small Cell Lung Cancer: Real World Long-Term Survival Results and Blood-Based Efficacy Biomarkers

Sameh Daher; Yaacov R Lawrence; Elizabeth Dudnik; Ekaterina Hanovich; Damien Urban; Nir Peled; Rossie Navon; Raya Leibowitz; Ariel Hammerman; Erez Battat; Teodor Gottfried; Amir Onn; Jair Bar

doi:10.3389/fonc.2021.625668

Nivolumab in Non-Small Cell Lung Cancer: Real World Long-Term Survival Results and Blood-Based Efficacy Biomarkers

Front Oncol. 2021 Jul 21:11:625668. doi: 10.3389/fonc.2021.625668. eCollection 2021.

Authors

Affiliations

¹ Thoracic Cancer Unit, Institute of Oncology, Sheba Medical Center, Tel HaShomer, Israel.
² Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
³ Institute of Oncology, Shamir Medical Center, Zerifin, Israel.
⁴ Department of Pharmaceutical Technology Assessment, Clalit Health Services Headquarters, Tel Aviv, Israel.

Abstract

Objectives: We aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).

Materials and methods: A chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and 'derived NLR' (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.

Results: 35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, p<0.001). In univariate and multivariate analysis, dNLR, albumin and LDH correlated significantly with OS. No variables correlated significantly with DC6 in multivariate analysis. Based on albumin and LDH, we produced a score called CLAS (combined LDH and albumin score), including four prognostic groups of patients. Patients having low albumin and high LDH had the worst prognosis.

Conclusion: In real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.

Keywords: NSCLC; biomarker; long term survival; nivolumab; real life data.