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.

Purpose Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS). Results Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (p = 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%–56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7–13.1 months) with ICI alone versus 13.8 months (95%CI 9.5–18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.556; p = 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (p = 0.016), patients with ECOG PS = 0 (p = 0.048), and patients with 1–2 metastatic sites (p = 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm. Conclusion Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.