Efficacy and safety of anlotinib with and without EGFR-TKIs or immunotherapy in the treatment of elder patients with non-small-cell lung cancer: a retrospective study

Abstract

Background: Anlotinib is a multitarget tyrosine kinase inhibitor for treating patients with advanced non-small cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of anlotinib in elder patients with advanced NSCLC.

Methods: Elder patients with advanced NSCLC who received anlotinib were enrolled. They were all age ≥ 65 years and with demonstrated records of EGFR gene status. All patients had received treatment with anlotinib or immune checkpoint inhibitors (ICIs)/EGFR-TKIs. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors (RECIST 1.1). Common Adverse Events Evaluation Criteria (CTCAE 4.03) were used to evaluate adverse drug reactions.

Results: A total of 91 patients were included in this study. We divided the patients into two groups (EGFR wild type: 60 patients; EGFR mutation: 31 patients). Among EGFR negative patients, the progression-free survival (PFS) for anlotinib monotherapy and anlotinib combination ICI therapy was 3.2 months and 5.0 months, respectively (P = 0.012). The difference in overall survival (OS) between monotherapy and combination therapy was also significant (9.5 vs. 18.4 months, respectively P = 0.010). Interestingly, we further analyzed differences between patients with hypertension and without hypertension, and found that hypertension was associated with better prognosis (5.7 vs. 1.4 months, P < 0.0001). In the EGFR mutation group, the PFS for anlotinib and EGFR-TKI combination treatment indicated better efficacy than that of anlotinib monotherapy (1.83 months vs. 7.03 months, respectively, P = 0.001). The median OS for monotherapy and combination therapy in the EGFR mutation group showed no statistical difference (28.34 months vs. 31.37 months, P = 0.223). The most common adverse reactions were hypertension, fatigue, and hand-foot syndrome, mainly of grade 1 or 2. No significant increase in adverse reactions was observed in patients ≥ 70 years of age.

Conclusions: Anlotinib treatment and combination regimens resulted in good efficacy and controllable adverse reactions in elder patients with advanced NSCLC.

Keywords: Angiogenesis; Non-small cell lung cancer; Prognosis; Tyrosine kinase inhibitors.

Fig. 1

Kaplan Meier estimates of progression-free survival (PFS) and overall survival (OS) according to type of anlotinib treatment modes in patients with EGFR negative A PFS in all EGFR negative NSCLC patients; B PFS in the anlotinib monotherapy and combination therapy groups (P = 0.012); C OS in all EGFR negative NSCLC patients; D OS in the anlotinib monotherapy and combination therapy groups (P = 0.010)

Fig. 2

Kaplan Meier estimates of progression-free survival (PFS) and overall survival (OS) according to type of anlotinib treatment modes in patients with EGFR mutations A PFS in all EGFR mutated NSCLC patients; B PFS in the anlotinib monotherapy and combination therapy groups (P = 0.001); C OS in all EGFR mutated NSCLC patients; D OS in the anlotinib monotherapy and combination therapy groups (P = 0.223)

Fig. 3

The comparison of the ration of the patients with the common adverse reactions (hypertension, hand-foot syndrome, and fatigue) and without them during anlotinib and combined with ICIs treatment in EGFR gene negative NSCLC. Then, stratification analysis of PFS of anlotinib between patients with and without the common adverse reactions. A The ratio of the patients with hypertension between anlotinib and combined with ICIs treatment was 50% and 58.9%, respectively (P = 0.049). B PFS of patients with and without hypertension in EGFR gene negative NSCLC was 5.7 months and 1.4 months (P < 0.0001). C The ratio of the patients with hand-foot syndrome between anlotinib and combined with ICIs treatment was 47.4% and 38%, respectively (P = 0.118). D PFS of patients with and without hand-foot syndrome was 4.9 months and 2.1 months (P = 0.431). E The ratio of the patients with fatigue between anlotinib and combined with ICIs treatment was 31.5% and 40.9% (P = 0.465). F PFS of patients with and without fatigue was 5.3 months and 3.2 months (P = 0.575)

Fig. 4

The comparison of the ration of the patients with the common adverse reactions (hypertension, hand-foot syndrome, and fatigue) and without them during anlotinib and combined with ICIs treatment in EGFR mutated NSCLC. Stratification analysis of PFS of anlotinib between patients with and without the common adverse reactions. A The ratio of the patients with hypertension between anlotinib and combined with ICIs treatment was 44.5% and 46.2%, respectively (P = 0.924). B PFS of patients with and without hypertension in EGFR mutated NSCLC was 2.5 months and 2.1 months (P = 0.716). C The ratio of the patients with hand-foot syndrome between anlotinib and combined with ICIs treatment was 44.5% and 38.5%, respectively (P = 0.739). D PFS of patients with and without hand-foot syndrome was 2.8 months and 2.1 months (P = 0.226). E The ratio of the patients with fatigue between anlotinib and combined with ICIs treatment was 38.9% and 46.2% (P = 0.685). F PFS of patients with and without fatigue was 2.5 months and 2.1 months (P = 0.835)

Fig. 5

Compared the incidence of the common adverse events (hypertension, hand-foot syndrome, and fatigue) between the ages of ≥ 70 years and < 70 years according to EGFR gene negative and mutation groups. A–C There was no statistical difference in the proportion of EGFR-negative patients who experienced the common adverse events at age ≥ 70 years and < 70 years. D–F There was also no statistical difference in the proportion of EGFR-mutation patients