A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer.

Alofanib is a small-molecule allosteric extracellular FGFR2 inhibitor. We report safety and preliminary efficacy from the first-in-human phase 1b study of alofanib in heavily pretreated patients with advanced gastric cancer. The standard dose-escalation design 3+3 aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Alofanib was administered daily intravenously 5 days on, 2 days off. There were five dose levels (50-350 mg/m2). All patients received alofanib until disease progression or unacceptable toxicity. 21 patients were enrolled. Patients were predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 19% had ECOG PS 2, and were heavily pretreated (86% had previous 2 and more treatment lines). During dose escalation, no dose-limiting toxicities were observed, and MTD was not defined. 15 (71.4%) patients had at least one adverse event associated with the treatment (TRAE). Grade 3 or higher TRAEs were observed in 6 patients (28.6%). The most common TRAEs included reactions immediately after administration, diarrhea, thrombocytopenia, arthralgia, and headache. The median progression-free survival and overall survival was 3.63 (95% CI 1.58-5.68) and 7.0 (95% CI 3.82-10.18) months, respectively. The 6- and 12-month overall survival rates were 57.1% and 33.3%. Disease control rate was 68% with one durable partial response. The MTD has not been reached and dose of 350 mg/m2, 5 days on, 2 days off has been declared as RP2D. Alofanib showed acceptable tolerability and preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer. (ClinicalTrials.gov identifier: NCT04071184).

Real-world treatment patterns among patients with advanced gastric cancer in Russia: a chart review study.

Objective: Little evidence is available on the management of patients with metastatic and/or unresectable gastric cancer (mGC) after the failure of first-line treatment. This study presents real-world data on characteristics and treatment patterns of patients with mGC in Russia. Methods: Eligible patients were ≥18 years old, diagnosed with mGC ≥ January 1, 2012, received first-line chemotherapy followed by second-line chemotherapy or best supportive care (BSC), had ≥3 months of follow-up after the start of second-line chemotherapy or BSC (except in cases of death), and had not participated in a clinical trial. Data were summarized using descriptive statistics. Results: A total of 88 physicians provided data from 202 charts. Mean age at mGC diagnosis was 53.7 (standard deviation: 11.2) years; 70.8% of patients were male. Reasons for first-line treatment discontinuation included disease progression (50.5%) and adverse events/toxicity (39.1%). There were 52 unique treatment regimens prescribed in second-line; capecitabine (14.5%), paclitaxel (9.3%), and capecitabine + oxaliplatin (8.7%) were the most frequent. Reasons for second-line treatment discontinuation included disease progression (39.8%) and patient refusal to continue (37.5%). During 2nd-line treatment, the most common treatment-related symptoms were nausea/vomiting (75.0%), while pain (73.8%) was the most common disease-related symptom. Antiemetics (63.4%), chemotherapy (61.6%), non-narcotic analgesics (48.3%), endoscopy (45.9%), and nutritional support (35.5%) were most frequently used as supportive care. Conclusions: Second-line treatment patterns for patients with mGC in Russia are heterogeneous. Results of this study indicate the need for more intensive implementation of the most active regimens in second-line treatment of mGC according to international and national guidelines.