Efficacy and Safety of Anlotinib in Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Study

Abstract

Background: Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) independently developed by China, which can inhibit tumor angiogenesis and tumor cell proliferation. The ALTER 0303 study has suggested that anlotinib improved overall survival (OS) and progression-free survival (PFS) in the treatment of advanced non-small cell lung cancer (NSCLC). However, in the real world, the efficacy and safety of anlotinib is not clear. Although relevant retrospective studies have confirmed the efficacy and safety of anlotinib, the sample size is small. And the OS was not observed because of the follow-up time was short. Further studies are still essential to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC in real-world settings. Related studies have preliminarily shown that anlotinib combined with whole-brain radiotherapy (WBRT) can significantly prolong the survival of patients with brain metastases of NSCLC. This study also discusses the best treatment strategies of patients with brain metastases. Methods: A retrospective study was conducted on 206 patients with advanced NSCLC who had treated with anlotinib. The primary endpoints were PFS and OS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Kaplan-Meier survival curves were applied to evaluate the efficacy. Univariate analysis was performed by Log rank testing. Cox regression analysis was utilized to evaluate the significance of potential risk factors obtained from the univariate analysis. Results: The median PFS (mPFS) was 4.0 (95% CI: 3.607-4.393) months, univariate analysis revealed that patients with longer PFS included epidermal growth factor receptor (EGFR) mutation-negative, Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, no brain metastases, no liver metastases, no adrenal metastases, or ≤2 distant metastases. Cox regression analysis indicated that patients with EGFR-negative and ECOG PS ≤1 had longer PFS. The median OS (mOS) was 8(95% CI: 6.495-9.505) months. EGFR mutation-negative, previous thoracic radiation therapy, no brain metastases, or ≤2 distant metastases were independent positive predictors of OS. The results of Cox regression indicated that the patients without previous thoracic radiation therapy (hazard ratio: 1.855; 95% CI: 1.162-2.960; p=0.010) had shortened OS. The objective response rate was 10.2%, and the disease control rate was 78.2%. The main treatment-related adverse events (AEs) were generally tolerated. All AEs observed during the trial were controlled after dose reduction or symptomatic treatments, and no death was found to be associated with anlotinib. Conclusion: Anlotinib was well tolerated and effective in patients with advanced NSCLC. Patients with EGFR mutation-negative and ECOG PS ≤1 had longer PFS, and patients without previous thoracic radiation therapy (HR: 1.855, 95% CI 1.162-2.960; P = 0.010) had shorter OS. Further investigations are needed because of small sample.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…And the ORR, DCR, and median PFS were 10–16%, 78–80%, and 4.0–4.5 months, respectively. 30 , 31 The subgroup analysis in their study suggested that the median PFS of patients ≥60 years was 4.5 and 4.0 months and no statistical significance regarding PFS analysis was observed according to the age subgroup, which was consistent with that in our study and demonstrated that elderly patients could benefit from anlotinib monotherapy similar to the younger patients. Additionally, another independent factor that showed positive relevance to PFS identified in our study was the number of metastases sites.…”

The real‐world clinical outcomes and treatment patterns of patients with unresectable locally advanced or metastatic soft tissue sarcoma treated with anlotinib in the post‐ALTER0203 trial era

“…Although cancer patients with poor performance status may still benefit from antitumor treatment, 31 most cancer clinical trials had strict performance status (0 or 1) criteria, 32 such as the PALETTE, REGOSARC, and ALTER0203 studies 10,11,13 . Indeed, we found that patients ( n = 39, 18.7%) with an ECOG performance status of ≥2 had poor survival outcomes (Tables 4 and 5, Figure 2), which was consistent with the findings in patients with advanced non‐small cell lung cancer receiving anlotinib treatment 33,34 . From the data in Table 1, it was observed that ECOG performance status also generally determined the treatment strategy in clinical practice.…”

“…10,11,13 Indeed, we found that patients (n = 39, 18.7%) with an ECOG performance status of ≥2 had poor survival outcomes (Tables 4 and 5, Figure 2), which was consistent with the findings in patients with advanced non-small cell lung cancer receiving anlotinib treatment. 33,34 From the data in Table that ECOG performance status also generally determined the treatment strategy in clinical practice. Therefore, we conducted an ad hoc analysis to explore the survival difference in treatment patterns stratified by ECOG performance status.…”

Efficacy and safety of anlotinib combined with carboplatin and pemetrexed as first-line induction therapy followed by anlotinib plus pemetrexed as maintenance therapy in EGFR/ALK wild-type advanced non-squamous non-small cell lung cancer in China: a multicenter, single-arm trial

“…No new safety signals were observed in this study. The most common AEs were hypertension, neutropenia, bone marrow toxicity, and thrombocytopenia, in agreement with the known AE profile of anlotinib combined with chemotherapy (17,18,28,29).…”