Efficacy and safety of anlotinib plus programmed death-1 blockade versus anlotinib monotherapy as second or further-line treatment in advanced esophageal squamous cell carcinoma: A retrospective study

Abstract

BackgroundBoth anlotinib and programmed death-1 (PD-1) blockade have been approved for the second-line treatment of metastatic esophageal squamous cell carcinoma (ESCC). However, the combination of these two therapies has not been evaluated. This study investigated the efficacy and safety of anlotinib, a novel multitarget tyrosine kinase inhibitor targeting tumor angiogenesis, combined with PD-1 blockade as second or further-line treatment for advanced ESCC.MethodsBetween January 2019 and February 2021, 98 advanced ESCC patients receiving anlotinib plus PD-1 blockade or anlotinib monotherapy as second or further-line treatment at Henan Cancer Hospital were retrospectively analyzed. Patients receiving anlotinib plus PD-1 blockade were grouped as cohort A (n=48), while those receiving anlotinib monotherapy were grouped as cohort B (n=50). The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR) and toxicity. Furthermore, independent prognostic factors were identified by Cox regression analysis. A two-sided p-value of <0.05 was considered statistically significant.ResultsData was collected until May 1, 2021, with a median follow-up time of 9.30 months (8.23–10.37 months) in cohort A and11.10months (7.82–14.38 months) in cohort B. For patients with advanced ESCC, cohort A resulted in significantly longer PFS (5.40 vs. 3.00 months, P<0.001) and higher DCR (71.7% vs. 47.9%, P=0.019) than cohort B. The ORR indicated no significant difference between cohort A (23.9%) and cohort B (10.4%) (P=0.082). Adverse reactions were mainly grade1/2 in the two groups. Compared with cohort B, a significantly higher rate of grade 1–2 hypothyroidism was observed in patients in cohort A (P= 0.034). Three patients (6.3%) developed grade 1/2 immune-related pneumonia. There was no significant difference in the incidence of grade 3-4 toxicities. Multivariable Cox regression analysis showed that the drug regimen (P<0.001), Eastern Cooperative Oncology Group Performance Status (P=0.002), distant organ metastasis (P=0.008), and metastatic sites (P=0.032) were independent prognostic factors for PFS.ConclusionsAnlotinib plus PD-1 blockade showed promising anti-tumor activity and manageable toxicity as second or further-line treatment of advanced ESCC.

Combination therapy with toripalimab and anlotinib in advanced esophageal squamous cell carcinoma: A case report

“…Combination anti-PD-1 and targeted therapy is increasingly widely used for treatment of several malignancies such as gastric cancer, non-small cell lung cancer, and liver cancer, but its use is uncommon in ESCC[ 18 - 20 ]. Liu et al [ 5 ] retrospectively reviewed and analyzed 98 patients with advanced ESCC, wherein 48 patients were administered anlotinib plus an anti-PD-1 and remaining 50 patients received anlotinib monotherapy. Overall, patients receiving the combination therapy showed a longer PFS (5.4 vs. 3.0 mo) with a higher ORR (23.9% vs. 10.4%) than the patients receiving anlotinib monotherapy[ 5 ].…”

“…Liu et al [ 5 ] retrospectively reviewed and analyzed 98 patients with advanced ESCC, wherein 48 patients were administered anlotinib plus an anti-PD-1 and remaining 50 patients received anlotinib monotherapy. Overall, patients receiving the combination therapy showed a longer PFS (5.4 vs. 3.0 mo) with a higher ORR (23.9% vs. 10.4%) than the patients receiving anlotinib monotherapy[ 5 ]. Additionally, Tang et al [ 6 ] reported that a postoperative recurrent ESCC patient receiving a combination therapy of nivolumab and anlotinib showed CR.…”

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

“…Unlike sunitinib, zoledronic acid combined with radiation has a radiosensitizing effect on ESCC cells by blocking the cell cycle between S and G2/M phases, leading to increased cell death [ 118 ]. Anlotinib selectively inhibits VEGFR and contributes to the inhibition of tumor growth and metastasis, significantly improving PFS and disease control rate (DCR) in patients with advanced ESCC, and is now entering second-line and further-line treatment in ESCC [ 119 ]. Cisplatin-based CCRT toxicity is difficult to tolerate in patients with unresectable advanced ESCC, and RT combined with cisplatin and anlotinib or RT combined with paclitaxel and erlotinib can achieve better anti-esophageal cancer outcomes [ 110 , 120 ].…”