Efficacy and safety of anlotinib combined with PD‐1/PD‐L1 inhibitors as second‐line and subsequent therapy in advanced small‐cell lung cancer

Abstract

Objectives: Treatments for advanced small-cell lung cancer (SCLC) patients who are resistant to first-line chemotherapy are limited. Given that antiangiogenic agents and immune-checkpoint inhibitors (ICIs) can confer synergistic therapeutic benefits, combination therapy should be considered. We explored the efficacy and safety of combination therapy with anlotinib and programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors as second-line and subsequent therapy for advanced SCLC. Materials and Methods: We reviewed advanced SCLC patients at ShanghaiChest Hospital who had received anlotinib in combination with ICIs from November 2016 to November 2020 as second-and subsequent-line treatment.Patients with advanced SCLC who had received paclitaxel monotherapy as second-line treatment were included as the control group.Results: A total of 141 patients were included in the final analysis (40 in the combination therapy group and 101 in the paclitaxel monotherapy group). The median progression-free survival (PFS) times for the combination therapy and paclitaxel monotherapy groups were 3.40 and 2.83 months (p = 0.022), respectively, while the median overall survival (OS) times for the combination therapy and paclitaxel monotherapy groups were 8.20 and 5.87 months (p = 0.048), respectively. Hypertension and hepatic dysfunction were the most pronounced adverse events of combination therapy and two patients changed regimens due to severe fatigue and anorexia. Conclusion:The combination of anlotinib and PD-1/PD-L1 blockade has promising efficacy and safety as a second-line or subsequent therapy for SCLC.

The efficacy and safety of anlotinib for subsequent line treatment of small cell lung cancer: a systematic review and meta-analysis

“…After reading the full-text of the remaining 19 studies, 6 of them were further excluded as they were ongoing clinical trials and/or clinical trial designs. Finally, the remaining 13 studies [17][18][19][20][21][22][23][24][25][26][27][28][29] were included for this meta-analysis. The process of literature screening is shown in Figure 1.…”

“…The quality assessment results are summarized in Table 2. There were thirteen studies [17][18][19][20][21][22][23][24][25][26][27][28][29] assessed the efficacy results after anlotinib treatment. The OS and PFS were investigated in seven and thirteen studies, respectively.…”

“…The adverse events were reported in eleven studies. 17,19,[21][22][23][24][25][26][27][28][29] For non-RCT studies, three studies 19,22,28 were considered as poor quality due to a NOS score of less than seven stars, and the rest were found to be intermediate quality. For RCT studies, the specific randomization method was not mentioned in the included studies.…”

“…In this meta-analysis, there were 8 retrospective studies with single arms, [18][19][20][21][22]25,26,28 3 retrospective studies 17,24,29 with two arms, and 2 RCTs 23,27 with anlotinib versus control arms. This meta-analysis involved 779 patients.…”

“…One study used anlotinib as the maintain therapy after the first-line treatment for extensivestage SCLC, and it was excluded. Seven studies 17,18,[24][25][26][27]29 reported anlotinib was administrated after first-line treatments, and six [19][20][21][22][23]28 used anlotinib after second-line treatment of SCLC. The baseline characteristics of the included studies are shown in Table 1.…”