The current standard of care for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma is doublet platinum or taxane-based therapies. The current phase 2, single-arm, 2-stage trial conducted by the Big Ten Cancer Research Consortium (BTCRC-GI15-015) evaluated the efficacy, tolerability, and patient-reported outcomes of anthracycline-based triplets, including FOLFOX and nab-paclitaxel (FOLFOX-A) in chemotherapy-naïve unresectable, advanced gastric/GEJ adenocarcinoma; results of this trial were reported at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
In this 2-stage study, 12 patients were planned to be enrolled in stage I; stage II enrollment proceeded if ≥1 responses were achieved (treatment continued until disease progression or unacceptable toxicity if ≥4 responses were observed in stage II). The study enrolled patients with HER2-negative, chemotherapy-naïve, unresectable, advanced gastric/GEJ adenocarcinoma. Eligible patients received nab-paclitaxel (150 mg/m2), oxaliplatin (85 mg/m2), leucovorin (400 mg/m2), and 5-fluorouracil (2400 mg/m2) over 46 to 48 hours every 14 days. The primary efficacy end point was response rate.
A total of 39 patients were enrolled in the 2-stage study; 12 patients in stage I; following a 29% response rate in stage I, 27 patients were enrolled as planned in stage II. The median age of the study population (n = 39) was 63 years (range, 20-80 years), 29 (74%) were male.
Results of the total cohort of 39 patients that enrolled in stages I and II and started treatment with FOLFOX-A were reported. An overall response rate (ORR) of 42.9% was achieved, which exceeded the expected study target of 20%; the disease control rate was 80.0%. At median follow-up of 20 months, median progression-free survival (PFS) was 6.6 months (95% confidence interval [CI], 5.7-12.9) and the 12-month PFS rate was 27.5% (95% CI, 15.0%-50.5%); median overall survival (OS) was 10.5 months (95% CI, 8.9-21.7); the 12-month OS rate was 44.2% (95% CI, 29.7%-65.7%). There was no difference in efficacy outcomes (including ORR, PFS, and OS) between the gastric and GEJ patient cohorts.
The safety profile was as expected for the FOLFOX-A regimen. Treatment-related grade 3/4 toxicities occurred in ≥5% of patients, including peripheral sensory neuropathy (18.4%), anemia (18.4% each), decreased neutrophil count (15.8%), diarrhea (7.9%), fatigue (5.3%), nausea (5.3%), white blood cell decreased (5.3%).
Based on these results, it was concluded that the FOLFOX-A regimen was associated with a high response rate and expected toxicities and may be considered for patients with metastatic or advanced unresectable gastric, GEJ adenocarcinoma.
Source
Benson AB, Kocherginsky M, Murtaza Kasi P, et al. A phase II study of FOLFOX combined with nab-paclitaxel (FOLFOX-A) in the treatment of metastatic or advanced unresectable gastric, gastroesophageal junction adenocarcinoma: Big Ten Cancer Research Consortium—BTCRC-GI15-015. Presented at: 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, January 20-22, 2022. Abstract 283.
