Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer

Background: Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (C_trough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL C_trough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL C_trough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL C_trough for the responder.

Results: 52 patients were evaluated for analyses. The median ANL C_trough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL C_trough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUC_ROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL C_trough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL C_trough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group.

Conclusions: Considering these results, we propose that maintaining ANL C_trough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.