Second-Line Anlotinib Plus Toripalimab Demonstrates Safety, Efficacy in Advanced Gastric or Gastroesophageal Junction Carcinoma

Combination anlotinib-toripalimab in the second-line setting showed promising efficacy and favorable safety for gastric or gastroesophageal junction carcinoma, according to trial results. Anlotinib is an oral multi-targeting tyrosine kinase inhibitor (TKI), and toripalimab is a novel anti-PD-1 antibody.

The current recommended treatment in the second-line setting for patients with advanced relapsed gastric/gastroesophageal junction carcinoma is ramucirumab plus paclitaxel. However, Man Jiang, MD, The Affiliated Hospital of Qingdao University, Qingdao, China, and colleagues wrote the efficacy of this regimen “is unsatisfactory, with an objective response rate of 17% to 28% and progression-free survival of 2 to 4 months.” Therefore, there is an unmet need for new and effective second-line treatment options for this patient population.

This single-arm, single-center extension trial enrolled 62 patients with advanced relapsed gastric/gastroesophageal junction carcinoma who had only 1 prior line of systemic therapy. All patients received 12 mg of oral anlotinib daily for 2 weeks, followed by 1 week off, plus 240 mg of intravenous toripalimab once every 3 weeks. The primary end point was objective response rate. Secondary end points included progression-free survival and an exploratory end point was the correlation of potential biomarkers with clinical efficacy.

At data cutoff date of December 31, 2020, 32.2% of patients achieved a partial response, 56.7% achieved stable disease, and 8.1% had progressive disease. The objective response rate was 32.3% with a disease control rate of 91.9%. The progression-free survival was 4 months (95% confidence interval [CI], 3.2 to 4.8).

The most common treatment-related adverse events, occurring in >30% of patients, were fatigue (88.7%), hypertension (71.0%), pruritus (37%), and leukopenia (33.9%). There were 11.3% of patients who experienced grade 3 adverse events, including proteinuria, thrombocytopenia, and hypertension. Treatment cessation due to adverse events was required in 1 case. No grade 4 events or deaths occurred.

Study authors noted the results from this trial “suggested that the combination of anlotinib and toripalimab had promising efficacy for [gastric/gastroesophageal junction carcinoma] patients as second-line treatment.” Additionally, PD-L1 expression, tumor mutational burden, and FGFR2 mutation were identified as potential biomarkers for predicting the efficacy of this regimen.

Source:

Jiang M, Zhang C, Hu Y, et al. Anlotinib combined with toripalimab as second-line therapy for advanced, relapsed gastric or gastroesophageal junction carcinoma. The Oncologist. 2022, 27(11):e856-e869. doi:10.1093/oncolo/oyac136