A cohort study of the efficacy and safety of immune checkpoint inhibitors plus anlotinib versus immune checkpoint inhibitors alone as the treatment of advanced non-small cell lung cancer in the real world

Abstract

Background: Anlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and has been shown to have antitumor effects and synergistic antitumor effects with immunotherapy only in animal studies and in the 2nd-line treatment in small clinical trials. A real-world study with large sample to compare the efficacy and safety of anlotinib plus immune checkpoint inhibitors (ICIs) with ICIs alone in the multiline treatment of advanced non-small cell lung cancer (NSCLC) was urgently needed. Methods: The data of 535 advanced NSCLC patients were collected from January 1, 2018, to December 31, 2021. The patients were divided into 2 groups: (I) ICI monotherapy (230 patients); (II) ICI + anlotinib (305 patients). After propensity-score matching (PSM) to reduce the effects of biases and confounding variables, the progression-free survival time (PFS), occurrence of adverse events, disease control rate (DCR), and objective response rate (ORR) of the 2 groups were compared. The effects of clinical factors, including age, gender, gene mutations, tumor proportion score, metastases, and combined radiotherapy, were also analyzed. Results: After PSM, the baseline clinical characteristics were well balanced and the 2 group had a good comparability. Patients in the ICI + anlotinib group had significantly longer median PFS in both the 2nd-line treatment (7.73 vs. 4.70 months; P=0.003) and 3rd-line treatment (5.90 vs. 3.37 months; P=0.020), but the difference lacked statistical significance in the 1st-line treatment (8.40 vs. 5.20 months; P=0.229). The overall ^ ORCID: 0000-0001-6458-2458.median PFS of patients in the ICI + anlotinib group was also much longer than that of patients in the ICI monotherapy group (6.37 vs. 3.90 months; P<0.001). The ICI + anlotinib group also tended to have a higher DCR, a higher ORR, and a higher probability of severe adverse drug reactions during the treatment than the ICI monotherapy group, but the differences were not statistically significant. Combining ICI + anlotinib could improve the outcomes of patients with bone metastasis.Conclusions: Anlotinib + ICI therapy could have greater efficacy in the treatment of advanced NSCLC patients than ICI monotherapy. The probability of adverse events might increase in the combined treatment, but could be controlled.

Effectiveness of PD1/PD-L1 combined with anti-angiogenic drugs in patients with advanced nonsmall cell lung cancer: A systematic review and meta-analysis

“…The included studies[ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] in this analysis were conducted between January 2017 and September 2022 [ Table 1 ]. Of the 1720 studies, 17 met the inclusion and exclusion criteria, comprising 5 randomized controlled trials[ 21 , 25 , 34 , 35 , 36 ] and 12 retrospective cohort studies.…”

“…Thirteen studies[ 20 , 21 , 22 , 24 , 26 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 ] reported HR values of PFS between the PD-1/PD-L1 plus AAs and monotherapy in NSCLC patients. By heterogeneity test, I 2 = 75%, P < 0.00001, using the random-effect model (RE model), the results demonstrated a statistically significant prolongation of PFS in the PD-1/PD-L1 plus AAs group compared to the monotherapy group (HR = 0.61, 95% CI: 0.50–0.75, P < 0.00001), as shown in Figure 3 .…”

“…Fifteen studies[ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 ] reported RR values for ORR in NSCLC patients treated with either PD-1/PD-L1 combination AAs or monotherapy. A meta-analysis was conducted with a heterogeneity test revealing I 2 = 66% and P = 0.0002.…”

Combination of Bone-Modifying Agents with Immunotarget Therapy for Hepatocellular Carcinoma with Bone Metastases

“…Previous research has validated that the anti-PD-1 ICIs can prevent the differentiation of osteoclast precursor cells to osteoclasts by intercepting CCL2 generation, which contributes to enhanced anti-tumor immunity [ 31 ]. Pre-existing evidence has confirmed the positive effect of TKIs plus ICIs for patients with solid tumors and metastases [ 32 , 33 , 34 ]. However, limited clinical investigations have focused on the efficacy and safety of immunotargeted therapy and BMAs for metastatic HCC patients with BoM.…”

Real-world incidence and risk factors of pneumonitis in chemoradiation plus immune checkpoint inhibitors compared with chemoradiation alone in lung cancer: a retrospective cohort study

“…The introduction of immune checkpoint inhibitors (ICIs) has represented a milestone in lung cancer treatment that significantly improves the overall response and survival of lung cancer patients. They were recommended to use in advanced stage lung cancer patients in combination with chemotherapy or targeted therapy ( 1 ). But in locally advanced and inoperable non-small cell lung cancer (NSCLC) patients, concurrent chemoradiotherapy (cCRT) was still standard therapy according to National Comprehensive Cancer Network (NCCN) guideline version 4, 2023 ( 2 ).…”