In an Italian phase III study (ARMANI) reported in The Lancet Oncology, Randon et al found that switch maintenance with ramucirumab/paclitaxel was associated with significantly improved progression-free survival vs continuation of first-line oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric/gastroesophageal junction cancer.
Study Details
In the multicenter open-label trial, 280 patients with disease control after 3 months of first-line FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) were randomly assigned between January 2017 and October 2023 to receive maintenance paclitaxel at 80 mg/m² on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days (n =144) or continuation of FOLFOX or CAPOX for an additional 12 weeks followed by fluoropyrimidine monotherapy maintenance. The primary endpoint was progression-free survival.
Key Findings
Median follow-up was 43.7 months. Median progression-free survival was 6.6 months (95% confidence interval [CI] = 5.9–7.8 months) in the switch maintenance group vs 3.5 months (95% CI = 2.8%–4.2 months) in the control group (hazard ratio [HR] = 0.61, 95% CI = 0.48–0.79, P = .0002). Since the assumption of proportional hazards was violated, an analysis of 24-month restricted mean survival time (RMST) was performed; restricted mean progression-free survival was 8.8 months (95% CI = 7.7–9.9 months) in the switch maintenance group vs 6.1 months (95% CI = 5.0–7.2 months) in the control group (P = .0010).
Median overall survival was 12.6 months (95% CI = 11.5–15.0 months) in the switch maintenance group vs 10.4 months (95% CI = 8.0–13.1 months) in the control group (HR = 0.75, 95% CI = 0.58–0.96, P = .025). The proportional hazards assumption was violated; a 36-month RMST analysis showed restricted mean overall survival of 15.8 months (95% CI = 14.2–17.5 months) in the switch maintenance group vs 12.7 months (95% CI = 11.0–14.4 months) in the control group (P = .0090).
Grade ≥ 3 treatment-related adverse events occurred in 40% of the switch maintenance group vs 21% of patients in the control group; the most common in the switch maintenance group were neutropenia (26% vs 10% in control group), peripheral neuropathy (6% vs 7%), and hypertension (6% vs 0%). Serious adverse events occurred in 20% vs 11% of patients and were considered treatment-related in two patients in each group. No treatment-related adverse events led to discontinuation of treatment. No treatment-related deaths were observed.
The investigators concluded: “Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents.”
Filippo Pietrantonio, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Eli Lilly. For full disclosures of the study authors, visit www.thelancet.com.
