To observe the efficaly and safety of combination regimen of anlotinib with pemetrexed and carboplatin in patients with advanced lung adenocarcinoma with acquired resistance to tyrosine kinase inhibitor (TKI).

Patients with advanced lung adenocarcinoma with acquired TKI resistance were divided into control group and treatment group according to the treatment methods. Patients in the control group received intravenous infusions of pemetrexed disodium for injection (500 mg·m^-2) and carboplatin injection (dose cauculated based on area under the blood concentration-time curve 6 g·L^-1·min^-1) on the first day of each treatment cycle, with each 3 weeks as one cycle. On the basis of the control group, the treatment group was given anlotinib hydrochloride capsules, which were taken 10 mg orally continuously for 2 weeks starting from day 1 of each cycle, followed by a 1-week drug holiday. Each 3-week period constituted one treatment cycle. Both groups were continuously treated for 4 cycles or more. The therapeutic outcomes, tumor marker concentrations, and vascular endothelial growth factor (VEGF) levels, immune function, safety evaluation, and long-term efficacy were compared between the two groups.

A total of 102 cases were enrolled; there were 48 cases in control group and 54 cases in treatment group. Disease control rate of control group and treatment group were 64.58% (31 cases/48 cases) and 83.33% (45 cases/54 cases), respectively; the carbohydrate antigen 125 levels were (52.38±7.21) and (48.49±6.12) U·mL^-1, respectively; the carcinoembryonic antigen levels were (8.29±1.79) and (7.52±1.21) μg·L^-1, respectively; the neuron-specific enolase levels were (26.17±4.33) and (23.84±3.32) μg·L^-1, respectively; the VEGF-A levels were (95.38±10.76) and (89.47±11.32) pg·mL^-1, respectively; the VEGF-B levels were (87.41±9.76) and (82.63±8.13) pg·mL^-1, respectively; and the VEGF-C levels were (61.56±7.49) and (58.67±6.20) pg·mL^-1, respectively. Comparison of all measured parameters in the treatment group and control group demonstrated statistically significant differences (all P<0.05). Adverse event rate of control group and treatment group were 37.50% (18 cases/48 cases) and 42.59% (23 cases/54 cases) respectively; median progression-free survival were 16 and 21 months, respectively; overall survival were 22 and 34 months, respectively; compared between 2 groups, the differences of the above indicators were not statistically significant (all P>0.05).

The addition of anlotinib to pemetrexed and carboplatin in patients with TKI-acquired resistant advanced lung adenocarcinoma significantly enhances the efficacy and immunomodulation, and inhibits the tumor growth at the same time, with a good safety profile and long-term efficacy.