Clinical efficacy of Anlotinib combined with radiotherapy in treating brain metastases of lung cancer in male patients

Background: This study analyzed the clinical efficacy of the anti-angiogenic drug Anlotinib in combination with radiotherapy for the treatment of brain metastases in male lung cancer patients. Methods: From existing case records, a retrospective analysis was performed on data from 63 male lung cancer patients with brain metastases treated at our hospital between January 2019 and December 2023. Based on the different treatment methods recorded, of them, 33 patients underwent intensity-modulated radiotherapy (IMRT) alone (radiotherapy group), and 30 underwent Anlotinib combined with IMRT (combined treatment group). The clinical outcomes of both treatment approaches were compared. Results: The results showed that 1 month after treatment, the objective response rate (ORR) of intracranial tumors was relatively higher in the combined treatment group than in the radiotherapy group (70.00% vs. 48.48%), though the difference was not statistically significant (p > 0.05), while the incidence of progressive disease (PD) was significantly lower in the combined treatment group (6.67% vs. 33.33%; p < 0.05), indicating that the addition of Anlotinib significantly reduced disease progression (p < 0.05). Moreover, patients in the combined treatment group had a shorter duration of dehydrating medication use and faster headache relief compared to the radiotherapy group (p < 0.05), as well as significantly longer progression-free survival (PFS) and overall survival (OS) compared to the radiotherapy group (p < 0.001). Conclusions: In conclusion, these findings suggest that Anlotinib, when combined with radiotherapy, could enhance the therapeutic benefits of male lung cancer patients with brain metastases. Further large-scale randomized controlled trials are required to confirm these results.

Anlotinib; Intensity-modulated radiotherapy; Brain metastases of lung cancer

[1] Teixidor-Vilà E, Trallero J, Puigdemont M, Vidal-Vila A, Hernandez-Martínez A, Sais E, et al. Lung cancer survival trends and prognostic factors: a 26-year population-based study in Girona Province, Spain. Lung Cancer. 2024; 197: 107995.

[2] Neto EB, de Almeida Bastos DC, Yoshikawa MH, Figueiredo EG, de Assis de Souza Filho F, Prabhu S. Short-term predictors of stereotactic radiosurgery outcome for untreated single non-small cell lung cancer brain metastases: a restrospective cohort study. Neurosurgical Review. 2024; 47: 172.

[3] Jun J, Yuan L, Jie C, Xiao Z, Chao X, Shaojie L, et al. Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases. Journal of Nanobiotechnology. 2024; 22: 159.

[4] Lichao L, Jian W, Ying W, Lingjuan C, Ling P, Yawen B, et al. Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization. Journal of Experimental & Clinical Cancer Research. 2024; 43: 128.

[5] Toriduka D, Matsuo Y, Hanazawa H, Kishi N, Uto M, Mizowaki T. Validation of the lung-mol graded prognostic assessment (GPA) system for the prognosis of patients receiving radiotherapy for brain metastasis from non-small cell lung cancer. Cureus. 2024; 16: e57485.

[6] Pu X, Xiao Z, Li J, Wu Z, Ma Z, Weng J, et al. Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: a multicenter, randomized phase II trial. Lung Cancer. 2024; 191: 107538.

[7] Weng G, Fang W, Lin Y, Chen L, Su W. Clinical effect of anlotinib in combination with docetaxel in treating advanced non-small cell lung cancer. Cellular and Molecular Biology. 2024; 70: 212–216.

[8] Yin H, Hu Z, Yang J. Risk factors and nomograms for diagnosis and early death in patients with combined small cell lung cancer with distant metastasis: a population-based study. Journal of International Medical Research. 2024; 52: 1–16.

[9] Cheng Z, Cao W, Sun B. A global perspective: comprehensive study of epidemiology, risk factors, and disease associations of tracheal, bronchus, and lung cancer from 1990 to 2019. Clinica Chimica Acta. 2024; 558: 118083.

[10] Huang YC, Jiang N, Shen M, Lai GG, Tan AC, Jain A, et al. Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations. Cancer Research. 2024; 84: 2009–2020.

[11] Kuang L, Wang P, Zhou L, Li Y. Strategies and influencing factors for the treatment of advanced non-small cell lung cancer based on epidermal growth factor receptor tyrosine kinase inhibitors: a narrative review. Translational Cancer Research. 2024; 13: 5123–5140.

[12] Takashima K, Wakabayashi H, Murakami Y, Saiki A, Matsuzawa Y. Prognostic factors in Japanese EGFR mutation-positive non-small-cell lung cancer: a real-world single-center retrospective cohort study. Drugs-Real World Outcomes. 2024; 11: 603–615.

[13] Fukuda Y, Uchida Y, Ando K, Manabe R, Tanaka A, Sagara H. Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: a systematic review and meta-analysis. Respiratory Investigation. 2024; 62: 481–487.

[14] Tang M, Xu M, Wang J, Liu Y, Liang K, Jin Y, et al. Brain metastasis from EGFR-mutated non-small cell lung cancer: secretion of IL11 from astrocytes up-regulates PDL1 and promotes immune escape. Advanced Science. 2024; 11: 2306348.

[15] Xu J, Wang P, Li Y, Shi X, Yin T, Yu J, et al. Development and validation of an MRI-Based nomogram to predict the effectiveness of immunotherapy for brain metastasis in patients with non-small cell lung cancer. Frontiers in Immunology. 2024; 15: 1373330.

[16] Gao X, Liu T, Fan M, Sun H, Zhou S, Zhou Y, et al. The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study. World Journal of Surgical Oncology. 2024; 22: 89.

[17] Walters S, King AP, Case A, Maclean J, Powell J, Iqbal NS. 149 Stereotactic radiosurgery (SRS) for the treatment of brain metastases: Outcomes for lung cancer patients in South Wales. Lung Cancer. 2024; 190: 107710.

[18] Salari K, Lee JS, Ye H, Seymour ZA, Lee KC, Chinnaiyan P, et al. Long-term survival in patients with brain-only metastatic non-small cell lung cancer undergoing upfront intracranial stereotactic radiosurgery and definitive treatment to the thoracic primary site. Radiotherapy and Oncology. 2024; 196: 110262.

[19] Chang CL, Lin KC, Chen WM, Shia BC, Wu SY. Correspondence: intensity-modulated proton therapy versus intensity-modulated radiotherapy for inoperable esophageal squamous cell carcinoma: methodologic issues. Journal of Thoracic Oncology. 2024; 19: e2–e4.

[20] Luo J, Cheng K, Ji X, Gao C, Zhu R, Chen J, et al. Anlotinib enhanced CD8+ T cell infiltration via induction of CCL5 improves the efficacy of PD-1/PD-L1 blockade therapy in lung cancer. Cancer Letters. 2024; 591: 216892.

[21] Jin ZC, Chen JJ, Zhu XL, Duan XH, Xin YJ, Zhong BY, et al. Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study. EClinicalMedicine. 2024; 72: 102622.

[22] Yang X, Xiang M, Geng L, Wen Y, Du X. Anlotinib combined with S-1 in the third-line treatment of stage IV non-small cell lung cancer: study protocol for phase II clinical trial. Asian Pacific Journal of Cancer Prevention. 2019; 20: 3849–3853.

[23] Dou XJ, Ma RY, Ren DW, Liu Q, Yan P. Effectiveness and safety of anlotinib combined with PD-1 blockades in patients with previously immunotherapy treated advanced non-small cell lung cancer: a retrospective exploratory study. Lung Cancer. 2024; 15: 29–40.

[24] Cao B, Wang S, Li R, Wang Z, Li T, Zhang Y, et al. Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Biomedicine & Pharmacotherapy. 2022; 151: 113081.

[25] Jiang Y, Qiao S, Li L, Zhu X. Combination of radiotherapy and Anlotinib enhances benefit from immunotherapy to liver metastasis and abscopal tumor from lung cancer. International Immunopharmacology. 2024; 128: 111441.

[26] Zou B, Jiang H, Liu H, Lu J, Qiang HP, Lu MF, et al. Anlotinib combined with anti‐PD1 potentiates anti‐tumor immunity via immunogenic cell death and macrophage reprogramming. Advanced Therapeutics. 2023; 6: 2300141.

[27] Zhen H, Tian J, Li G, Zhao P, Zhang Y, Che J, et al. Raltitrexed enhanced antitumor effect of anlotinib in human esophageal squamous carcinoma cells on proliferation, invasiveness, and apoptosis. BMC Cancer. 2023; 23: 207.

[28] hu Y, Wang X, Chen Z, Zhou L, Di X, Fan P, et al. Anlotinib suppressed ovarian cancer progression via inducing G2/M phase arrest and apoptosis. Journal of Clinical Medicine. 2022; 12: 162.

[29] Wang Z, Ren B, Yang H, Qiu X, Wu Y, Xue C, et al. Efficacy and safety of anlotinib combined with immune checkpoint inhibitors and platinum-containing chemotherapy for later-line advanced non-small cell lung cancer: a retrospective three-arm real-world study using propensity-score matching. Frontiers in Oncology. 2024; 14: 1446950.

[30] Ma J, Song Y, Shou J, Bai Y, Li H, Xie X, et al. Anlotinib for patients with metastatic renal cell carcinoma previously treated with one vascular endothelial growth factor receptor-tyrosine kinase inhibitor: a phase 2 trial. Frontiers in Oncology. 2020; 10: 664.

[31] Shi Y, Ji M, Jiang Y, Yin R, Wang Z, Li H, et al. 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. Translational Lung Cancer Research. 2022; 11: 1051–1068.

[32] Fan P, Qiang H, Liu Z, Zhao Q, Wang Y, Liu T, et al. Effective low-dose anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy. Frontiers in Immunology. 2022; 13: 937924.

[33] Xia X, Pi W, Lan Y, Wu X, Lv D, Meng Y, et al. Synergistic antitumor effects of anlotinib combined with oral 5-Fluorouracil/S-1 via inhibiting Src/AKT signaling pathway in small-cell lung cancer. Analytical Cellular Pathology. 2022; 2022: 4484211.

[34] Kong C, Yu S, Qian P, Song X, Wen J, Jiang M, et al. Anlotinib combined with whole-brain radiotherapy in non-small cell lung cancer with multiple brain metastases that progressed or developed after at least one lines of prior treatment. Frontiers in Oncology. 2023; 13: 1169333.

[35] Wang L, Huang Y, Sun X. Sintilimab combined with anlotinib as first-line treatment for advanced sarcomatoid carcinoma of head and neck: a case report and literature review. Frontiers in Oncology. 2024; 14: 1362160.