In a single-institution phase Ib/II trial reported in The Lancet Oncology, Kim A. Reiss, MD, and colleagues found that maintenance treatment with niraparib/ipilimumab produced better 6-month progression-free survival rates than niraparib/nivolumab in patients with advanced pancreatic cancer without disease progression after ≥ 16 weeks of platinum-based chemotherapy.
Kim A. Reiss, MD
As stated by the investigators, “Establishing alternatives to lifelong chemotherapy for patients with advanced pancreatic cancer has been proposed to address chemotherapy resistance and cumulative toxicity. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in this setting, and concurrent immune checkpoint blockade could offer synergistic tumor control. The aim of this study was to test the safety and antitumor activity of maintenance with PARP inhibition combined with immune checkpoint blockade in patients with advanced pancreatic cancer who had a stable response to platinum-based chemotherapy.”
Study Details
In the open-label trial, 84 evaluable patients at Abramson Cancer Center, University of Pennsylvania, were randomly assigned between February 2018 and October 2021 to receive niraparib at 200 mg per day plus either nivolumab at 240 mg every 2 weeks or, after a manufacturer dosing update, 480 mg every 4 weeks (n = 44) or ipilimumab at 3 mg/kg every 4 weeks for four doses (n = 40). The primary efficacy endpoint was 6-month progression-free survival, with both groups compared to the null hypothesis rate of 44%.
KEY POINTS
- Progression-free survival rates at 6 months were 20.6% with niraparib/nivolumab and 59.6% with niraparib/ipilimumab.
- Median overall survival was 13.2 months and 17.3 months, respectively.
Progression-Free Survival
Median follow-up was 23.0 months (interquartile range = 15.0–31.5 months). Progression-free survival at 6 months was 20.6% (95% confidence interval [CI] = 8.3%–32.9%; P = .0002 vs null hypothesis) in the niraparib/nivolumab group and 59.6% (95% CI = 44.3%–74.9%; P = .045 vs null hypothesis) in the niraparib/ipilimumab group. Since the upper bound of the 95% confidence interval in the niraparib/nivolumab group did not include the null hypothesis rate of 44%, the combination was deemed inferior. Since the lower bound of the 95% confidence interval in the niraparib/ipilimumab group exceeded the null hypothesis rate, the combination was deemed superior.
In post hoc analysis, median progression-free survival was 1.9 months (95% CI = 1.4–2.3 months) in the niraparib/nivolumab group vs 8.1 months (95% CI = 5.5–10.6 months) in the niraparib/ipilimumab group. Median overall survival was 13.2 months (95% CI = 8.1–16.7 months) vs 17.3 months (95% CI = 12.8–21.9 months).
Adverse Events
The primary endpoint of 6-month progression-free survival was met in the niraparib plus ipilimumab maintenance group, whereas niraparib plus nivolumab yielded inferior progression-free survival. These findings highlight the potential for noncytotoxic maintenance therapies in patients with advanced pancreatic cancer.— Kim A. Reiss, MD, and colleagues
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Among 91 patients who received at least one dose of study medication, grade ≥ 3 treatment-related adverse events occurred in 10 (22%) of 46 in the niraparib/nivolumab group vs 23 (50%) of 45 in the niraparib/ipilimumab group; the most common were hypertension (8%), anemia (4%), and thrombocytopenia (4%) in the former group and fatigue (14%), anemia (11%), and hypertension (9%) in the latter. Treatment-related serious events occurred in 11% vs 24% of patients. Grade 3 immune-mediated adverse events (no grade > 3 events observed) occurred in one patient (2%; colitis) vs 6 patients (13%; rash in 3, pneumonitis in 2, colitis in 1). No treatment-related deaths were reported.
The investigators concluded, “The primary endpoint of 6-month progression-free survival was met in the niraparib plus ipilimumab maintenance group, whereas niraparib plus nivolumab yielded inferior progression-free survival. These findings highlight the potential for noncytotoxic maintenance therapies in patients with advanced pancreatic cancer.”
Dr. Reiss, of the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Institutes of Health Funding, Bristol Myers Squibb, GlaxoSmithKline, and others. For full disclosures of the study authors, visit thelancet.com.
