Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib

Abstract

Background: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) has a low 10-year patient-survival rate and is challenging to treat. Lenvatinib is a multikinase inhibitor approved for the treatment of RR-DTC. This study aims to assess Eastern Cooperative Oncology Group performance status (ECOG PS) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for patients with RR-DTC treated with lenvatinib. Methods: In this retrospective analysis of the Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), patients randomly assigned to receive lenvatinib were classified according to baseline ECOG PS (0 or 1) or baseline NLR (≤3 or >3). The effects of baseline ECOG PS and NLR on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. In addition, the effects of baseline ECOG PS on the change in diameter of target lesions and correlations between baseline NLR and the sums of the diameters of target lesions were calculated. Results: Among patients who received lenvatinib, patients with a baseline ECOG PS of 0 had statistically improved PFS (hazard ratio [HR] 0.52; 95% confidence interval [CI 0.35-0.77]; p = 0.001), OS (HR 0.42 [CI 0.26-0.69]; p = 0.0004), and ORR (odds ratio [OR] 3.51 [CI 2.02-6.10]; p < 0.0001) compared with patients with a baseline ECOG PS of 1. Patients who received lenvatinib with a baseline NLR ≤3 also had improved PFS (HR 0.43 [CI 0.29-0.65]; p < 0.0001) and OS (HR 0.48 [CI 0.29-0.78]; p = 0.0029) versus patients with a baseline NLR >3. Moreover, patients with a baseline NLR ≤3 had a trend toward increased ORR (OR 1.57 [CI 0.94-2.64]; p = 0.08) compared with patients with a baseline NLR >3. Treatment-emergent adverse events were generally similar among patients who received lenvatinib, irrespective of patients' ECOG PS at baseline. Conclusion: Lower ECOG PS and NLR may provide prognostic value for improved efficacy in patients with RR-DTC. ClinicalTrials.gov no. NCT01321554.

Keywords: ECOG; NLR; differentiated thyroid cancer; lenvatinib; tumor size.

Conflict of interest statement

M.H.T. has performed consulting, is an advisory board member, and is on the speakers' bureaus for Bristol Myers Squibb and Eisai (honoraria). He is a consulting/advisory board member for Array Biopharma, Loxo Oncology, Blueprint Medicines, Bayer, Sanofi/Genzyme, Novartis, Arqule, and Merck (honoraria).

S.T. has received grants and personal fees from Eisai, Taiho, MSD, Chugai, Bayer, and AstraZeneca; and grants from Novartis.

J.C. has a scientific consultancy role (speaker and advisory roles) with Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, ITM, Sirlex, and Merck Serono. J.C. has received research grants from Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, and Bayer.

M.T. has received grants and personal fees from Eisai, MSD, Bristol Myers Squibb, Rakuten Medical, Pfizer, AstraZeneca, Bayer, and Ono Pharmaceutical. Personal fees from Merck, Serono, and LOXO.

S.L. has received research funding (inst) from Novartis and Sanofi Genzyme. She is an advisory board member for Eisai and Bayer.

N.K. reports grants and nonfinancial support for research funding from Eisai Co., Ltd, during the conduct of the study. Grants for research funding were received from AstraZeneca Co., Ltd, Bristol Myers Squibb, Pfizer Co., Ltd, and Chugai Pharmaceutical Co., Ltd. Grants and nonfinancial support for research funding were received from Ono Pharmaceutical Co., Ltd, outside the submitted work. Honoraria were received from Ono Pharmaceutical Co., Ltd, Bristol Myers Squibb, Merck Biopharma, AstraZeneca Co., Ltd, Merck Sharp & Dohme, Eisai, and Bayer.

C.E.D. is an employee of Eisai.

R.X. is an employee of Eisai.

B.R. has served in a consulting/advisory role for Eisai and LOXO; received honoraria from Eisai; and claims travel, accommodations, or expenses from Eisai and LOXO.

S.S. has served in a consulting/advisory role for Fortress Biotech and received grant support from Exelixis.

M.A.H. has served in a consulting role, is an advisory board member for Corcept and HRA Pharma (honoraria), and has received research support from Exelixis.

R.E. has served in a consulting/advisory role for Eisai, Exelixis, Sanofi Genzyme, and LOXO, and has served on speakers' bureaus for Eisai, Exelixis, Sanofi Genzyme, and LOXO.

L.J.W. has served in a consulting/advisory role with Bayer, Eisai, LOXO, and Merck.

Figures

FIG. 1.

Kaplan–Meier plots of PFS (A) and OS (B) in patients randomly assigned to receive lenvatinib, and with a baseline ECOG PS of 0 or 1. OS and PFS medians were calculated by Kaplan–Meier estimates, and the corresponding CIs were calculated with a generalized Brookmeyer and Crowley method. The HRs were estimated from an unstratified Cox proportional hazard model, and p-values were based on an unstratified log-rank test. CI, 95% confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; NE, not estimable; OS, overall survival; PFS, progression-free survival.

FIG. 2.

Percentage change from baseline to postbaseline nadir in the sums of diameters of target lesions in patients randomly assigned to receive lenvatinib, and with a baseline ECOG PS of 0 (A) or 1 (B). n = the number of patients with both baseline and at least 1 postbaseline target lesion assessment. Arrows indicate the 30% threshold for partial response, according to RECIST version 1.1. RECIST, Response Evaluation Criteria In Solid Tumors.

FIG. 3.

Kaplan–Meier plots of PFS (A) and OS (B) in patients randomly assigned to receive lenvatinib by NLR (≤3 or >3). OS and PFS medians were calculated by Kaplan–Meier estimates, and the corresponding 95% CIs were calculated with a generalized Brookmeyer and Crowley method. The HRs were estimated from an unstratified Cox proportional hazard model, and p-values were based on an unstratified log-rank test. NLR, neutrophil-to-lymphocyte ratio.

FIG. 4.

Correlation between baseline sums of diameters of target lesions and NLR in patients randomly assigned to receive lenvatinib (log scales).