Peripheral blood indices to predict PFS/OS with anlotinib as a subsequent treatment in advanced small-cell lung cancer

Abstract

Objective: In the phase II ALTER-1202 (NCT03059797) trial, anlotinib significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced small-cell lung cancer (SCLC) who underwent at least 2 previous chemotherapy cycles, when compared with a placebo group. To identify potential factors for predicting efficacy and prognosis with anlotinib treatment, we analyzed hematological indices at baseline and adverse events (AEs) over the course of anlotinib treatment. Methods: Data were collected from March 2017 to April 2019 from a randomized, double-blind, placebo-controlled, multicenter, phase II trial of anlotinib. Eligible patients were randomly assigned 2:1 to receive anlotinib or placebo until disease progression, intolerable toxicity, or withdrawal of consent. The patients received anlotinib (12 mg) or an analogue capsule (placebo) orally once daily for 14 days every 3 weeks. The hematological indices at baseline and AEs that occurred in the initial 2 treatment cycles were recorded. The Kaplan-Meier test and Cox regression model were used to assess survival differences. Results: A total of 82 patients (81 patients with complete data) were randomly assigned to receive anlotinib, with 38 receiving a placebo as a control. Multivariate analysis indicated that an elevated neutrophil to lymphocyte ratio > 7.75 and lactate dehydrogenase > 254.65 U/L at baseline were independent risk factors for PFS; basal elevated aspartate aminotransferase > 26.75 U/L, neuron specific enolase > 18.64 ng/mL, and fibrinogen > 4.645 g/L were independent risk factors for OS. During treatment, elevated γ glutamyltransferase and hypophosphatemia were independent predictors for a poor PFS, and elevated γ-glutamyl transferase and hypercholesterolemia were independent factors for OS. Conclusions: Our study preliminarily defined potential factors that affected the PFS and OS at baseline and during anlotinib treatment in patients with advanced SCLC. Our findings provide a basis for screening the dominant population and for dynamic efficacy monitoring with anlotinib therapy.

Inflammation‐based prognostic scoring system for predicting the prognosis of advanced small cell lung cancer patients receiving anlotinib monotherapy

“…Our study found that post‐NLR elevation was an independent prognostic factor of PFS but not for OS, as Cuicui Zhang et al described. 10 Although we found similar results in this study but did not share the same cut‐off value, which is 240.56 in SCLC and 205.63 in NSCLC, the conclusion from our previous study about NSCLC patients receiving anlotinib indicated that high pre‐PLR was related to poor outcome. 7 This phenomenon revealed the existence of different tumors with different cutoff values and the possibility of the difference being caused by insufficient sample capacity.…”

“…It could be due to the various follow-up treatments or other unknown factors. Our study found that post-NLR elevation was an independent prognostic factor of PFS but not for OS, as Cuicui Zhang et al described 10. Although we found similar results in this study but did not share thesame cut-off value, which is 240.56 in SCLC and 205.63 in NSCLC, the conclusion from our previous study about NSCLC patients receiving anlotinib indicated that high pre-PLR was related to poor outcome.…”

“… 8 , 9 Besides that, studies pointed out that some hematological indicators of inflammation and nutrition are connected with the efficacy of SCLC treatment, including NLR and prognostic nutritional index (PNI). 10 , 11 Anlotinib presents some good responses in SCLC and NSCLC and shares several predicted factors, such as NLR. A prognostic scoring system from our earlier research based on NLR and PLR illustrated the different prognoses in NSCLC patients treated with anlotinib.…”

“…Some adverse reactions to anlotinib treatment, such as hypertension, hand–foot syndrome, and tumor cavitation, may act as prognostic factors in SCLC, which resembles NSCLC 8,9 . Besides that, studies pointed out that some hematological indicators of inflammation and nutrition are connected with the efficacy of SCLC treatment, including NLR and prognostic nutritional index (PNI) 10,11 . Anlotinib presents some good responses in SCLC and NSCLC and shares several predicted factors, such as NLR.…”

Successful Treatment of a Patient With Multiple-Line Relapsed Extensive-Stage Small-Cell Lung Cancer Receiving Penpulimab Combined With Anlotinib: A Case Report

“…In addition, anlotinib is an oral multi-target tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and c-Met ( 5 , 6 ). The ALTER1202 study ( 7 , 8 ) showed that anlotinib could be a third-line standard treatment for patients with ES-SCLC for whom chemotherapy failed.…”