Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non–Small-Cell Lung Cancer After Previous Systemic Treatment Failure—A Retrospective Study

Abstract

BackgroundPre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.MethodsSixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1–14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.ResultsWith a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3–4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.ConclusionAnti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…Regarding the safety profile of anlotinib in elderly patients, the most common adverse reactions during anlotinib administration manifested as hypertension, fatigue, HFS, diarrhea, and loss of weight, which were the frequently experienced adverse reactions of antiangiogenic targeted drugs clinically. 33 However, it should be noted that the incidence of hypertension in our study seemed to be higher than that in the ALTER0303 trials, though a considerable proportion of the patients in our study were treated with the initial dosage of 10 mg anlotinib, especially the incidence of grade ≥3 hypertension (18.1% versus 13.2%). The possible explanation could be the elderly patients in our study.…”

“…Pembrolizumab, nivolumab, sintilimab, and camrelizumab were proved to be effective for previously treated patients with advanced NSCLC in subsequent-line therapy. 33 Consequently, elderly patients with previously treated NSCLC were able to choose the immunotherapy as the subsequent-line treatment when they failed anlotinib administration, which might prolong the survival of the patients to some extent.…”

Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer

“…Indeed, these therapeutic strategies have already been applied in clinical practice. Wang et al showed that the median PFS and OS were 6.9 months and 14.5 months in 67 NSCLC patients treated with anlotinib plus anti-programmed death-1 (PD-1) antibody after previous systemic treatment (26).Thus, we performed a retrospective analysis of realworld data to investigate the efficacy of anlotinib used alone and in combination with other agents in advanced NSCLC, with special attention to the combination of anlotinib with immunotherapy.…”

Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification

“…Anlotinib combined with nivolumab yielded favorable results, and the patient achieved a PR for more than 15 months. Similarly, two recent studies with small sample sizes have reported that the combination of anlotinib and anti-PD-1 drugs has promising efficacy and manageable toxic effects in patients with advanced lung adenocarcinoma and lung squamous cell carcinoma (12,30). The potential explanation for this synergistic effect is anlotinib may improve the ratio of CD8+ T cells/Foxp3+ cells in tumors by suppressing VEGFR-AKT signaling and thus improve immunotherapy effectiveness (31).…”