| BackgroundLung cancer is the malignant tumor with the highest morbidity and mortality in China and even in the world.The recurrence and metastasis of advanced lung cancer is still the leading cause of cancer-related deaths.Anlotinib is a multi-target anti-angiogenic agent approved for the third-line treatment of advanced NSCLC.In recent years,immune checkpoint inhibitor(ICI),especially targeted programmed death-1(PD-1)and its ligand(programmed death-ligand 1,PD-L1),the emergence of inhibitors has brought new hope for NSCLC patients,but the primary and secondary resistance of some patients to immune checkpoint inhibitors limits the use of single-agent ICI.With the in-depth study of the mechanism of tumor occurrence and development,it is believed that the combination of anti-angiogenic drugs and immunotherapy has a synergistic anti-tumor effect.At present,clinical trials of related anti-angiogenesis combined immunotherapy are ongoing.However,the study of anlotinib combined with immune checkpoint inhibitors for advanced non-small cell lung cancer chemotherapy regimens still lacks more real-world clinical data.ObjectiveThrough retrospective analysis,to observe the short-term efficacy and safety of two treatments of anlotinib hydrochloride and anlotinib hydrochloride combined with immune checkpoint inhibitors in the treatment of advanced NSCLC,so as to provide reference for the selection of treatment options for patients with advanced non-small cell lung cancer.MethodsCollected clinical data of patients with non-small cell lung cancer who received anlotinib combined with immune checkpoint inhibitors or treated with anlotinib alone from November 2018 to January 2021 in the Department of Oncology,First Affiliated Hospital of Xinxiang Medical College.These patients has used at least two cycles of anlotinib combined with immune checkpoint inhibitors or anlotinib alone.Observe the clinical efficacy and adverse reactions after the drug is used.Record the clinical data of the patient,including: gender,age,ECOG score,smoking status,pathological type,distant metastatic organs,treatment plan and number of medication lines,etc.The curative effect is evaluated after 2 cycles of treatment(according to the RECIST1.1 standard),and the various toxic and side effects of the patient during the medication process are evaluated(according to the CTCAE4.0 standard).Main observation indicators: Progression-free survival(PFS);secondary indicators: objective response rate(ORR),disease control rate(DCR),changes in adverse reactions(AEs).Results1.Follow-up until January 31,2021,a total of 68 patients were enrolled according to the inclusion and exclusion conditions,including 40 patients in the anlotinib monotherapy group,with 7.5% ORR and 85% DCR,and 28 patients in the anlotinib combined immunocheckpoint inhibitor group,with 28.6% ORR and 89.3% DCR.There were 25 cases of ≤2 line administration,13 cases of single drug group(ORR 7.7%,DCR 84.6%),12 cases of combined drug group(ORR 50.0%,DCR 83.3%).There were 27 cases of3-line administration,18 cases of single drug group(ORR 5.6%,DCR 77.8%),9 cases of combined drug group(ORR 44.4%,DCR 100%).There were 16 cases of >3-line administration,9 cases of single drug group(ORR 0%,DCR 100%),7 cases of combined drug group(ORR 0%,DCR 85.7%).After analysis,the ORR of single drug group,combination drug group and ≤3 line drug group in all cases had statistical significance(P< 0.05),while DCR of all treatment groups had no statistical significance(P > 0.05).2.Univariate analysis was used to compare the progression-free survival time between the two groups.The results showed that medication regimen and ECOG score had influence on PFS.The median progression-free survival(PFS)of the monotherapy group and the combination group were 3.0 months and 4.1 months(P=0.018),and the median PFS of ECOG 0 score and ECOG 1-2 score were 4.5 months and 3.5 months(P=0.031),respectively.3.The univariate analysis of the progression-free survival of the two groups with different number of medication lines and deletion of gene mutations showed that the m PFS of the single-drug group was 3.5 months for patients ≤2 line medication,and the m PFS of the combined group was 4.9 months(P<0.05).The m PFS of the single-drug group was 3.0months for the 3-line patients,and the m PFS of the combination group was 4.7 months(P<0.05).The m PFS of the single-agent group was 3.9 months in the >3-line medication patients,and the m PFS of the combined group was 3.3 months(P>0.05).After excluding the patients with gene mutation,the m PFS of the single-agent group was 3.4 months,and the m PFS of the combination group was 4.6 months(P<0.05).4.Cox multivariate analysis showed pathological types(HR=4.623,95% CI:1.847～11.572,P=0.001),smoking history(HR=0.276,95% CI:0.105～0.721,P=0.009),ECOG score(HR=0.344,95% CI:0.162～0.728,P=0.005),gene mutation(HR=0.393,95% CI:0.171～0.903,P=0.028)had an effect on the median PFS.5.Adverse reactions in both groups were controllable.Grade 3-4 adverse reactions occurred in 5 cases(12.5%)of the single drug group and 4 cases(14.3%)of the combined drug group,and there was no death event caused by adverse drug reactions.Conclusion1.Anlotinib hydrochloride combined with immune checkpoint inhibitors in the treatment of advanced non-small cell lung cancer has longer PFS and higher ORR in patients ≤3 line medication,and the adverse reactions of the combined medication are safe and controllable.However,there was no significant difference between the combined group and the monotherapy group for patients above the third line.2.In patients with advanced non-small cell lung cancer,the treatment of anlotinib hydrochloride combined with immune checkpoint inhibitors should be started as soon as possible. |
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