Background: PLATFORM is a prospective, open-label, multicentre, adaptive phase II trial assessing maintenance therapy in patients with advanced HER2-negative oesophagogastric adenocarcinoma after platinum-based first-line chemotherapy.
Patient and methods: After 18 weeks of platinum-based chemotherapy, patients with response or stable disease were randomised to surveillance (4 weekly visits) or rucaparib 600 mg tablet twice daily every 28 days. The primary endpoint was progression-free survival (PFS) (prespecified P value of 0.025). Secondary endpoints were safety and overall survival (OS). Exploratory translational analyses of homologous recombination deficiency (HRD) and somatic gene profiling are also reported.
Results: A total of 125 patients were randomised (surveillance: 62, rucaparib: 63). The median follow-up was 41 months. Median PFS was 2.8 months for surveillance and 4.2 months for rucaparib [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.49-1.02, P = 0.031]. There was no difference in OS (HR 1.15, 95% CI 0.77-1.72, P = 0.247). Grade ≥3 adverse events (AEs) occurred in 23% of surveillance and 32% of rucaparib patients. Treatment-related AEs were reported in 84% of patients in the rucaparib arm; 22% of which were grade 3-4. Most frequent grade 3-4 AEs were anaemia, fatigue, infection, and neutropenia. Adequate tissue for HRD analysis was available in 51/125 (40.8%) patients (surveillance: 20, rucaparib: 31). Five patients (9.8%) were HRD-positive, 41 (80.4%) HRD-negative, and 5 (9.8%) had inconclusive results. Among HRD-positive patients, four were treated with rucaparib and had PFS durations of 2.6, 3.0, 8.3, and 10.6 months, respectively. TP53 was the most frequently detected somatic alteration, followed by SMARCA4 and ARID1A.
Conclusion: Compared with surveillance, maintenance rucaparib following first-line chemotherapy in patients with advanced HER2-negative OGA did not significantly improve PFS with no observed difference in OS. Translational analyses were limited by small sample size, and no clear associations with clinical outcomes were identified.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)