In the Danish single-institution phase II CheckPAC study reported in the Journal of Clinical Oncology, Chen et al found that the combination of nivolumab and ipilimumab plus stereotactic body radiotherapy (SBRT) improved the clinical benefit rate vs nivolumab plus SBRT in patients with refractory metastatic pancreatic cancer.
In the open-label study, 84 patients at Herlev and Gentofte Hospital were randomly assigned between November 2016 and December 2019 to receive SBRT at 15 Gy on day 1 plus nivolumab at 3 mg/kg on day 1 and once every 2 weeks (n = 41) or the same nivolumab regimen plus ipilimumab at 1 mg/kg on day 1 and once every 6 weeks (n = 43). The primary endpoint was the clinical benefit rate.
Clinical Benefit Rate, Responses, and Survival
Median follow-up was 4.1 months (95% confidence interval [CI] = 3.7–5.8 months). In the intent-to-treat population, clinical benefit was achieved in 7 patients (17.1%, 95% CI = 8.0%–30.6%) in the nivolumab group vs 16 patients (37.2%, 95% CI = 24.0%–52.1%) in the nivolumab/ipilimumab group. Partial responses were observed in 1 (2.4%) vs 6 patients (14.0%), and stable disease was observed in 6 (14.6%) vs 10 patients (23.3%); no complete responses were observed. The one objective response in the nivolumab group lasted 4.6 months. Median response duration in the nivolumab/ipilimumab responders was 5.4 months (95% CI = 4.2 months–not reached).
KEY POINTS
- The nivolumab/ipilimumab group had a higher clinical benefit rate.
- More objective responses were observed in the nivolumab/ipilimumab group.
Median overall survival was 3.8 months (95% CI = 3.1–5.8 months) vs 3.8 months (95% CI = 2.8–6.5 months), with rates at 6 and 12 months of 29.3% vs 32.6% and 7.3% vs 14.0%. Median progression-free survival was 1.7 months (95% CI = 1.6–1.8 months) vs 1.6 months (95% CI = 1.6–2.8 months).
Among all patients, clinical benefit was not associated with PD-L1 tumor proportion score or combined positive score ≥ 1%. Decreased serum interleukin-6, interleukin-8, and C-reactive protein levels during treatment were associated with better overall survival.
Adverse Events
Treatment-related adverse events of any grade occurred in 87.8% of patients in the nivolumab group vs 74.4% of the nivolumab/ipilimumab group. Grade ≥ 3 treatment-related adverse events occurred in 24.4% vs 30.2% of patients; the most common (> 5% of patients) were fatigue (9.8%) in the nivolumab group and diarrhea (11.6%), fatigue (9.3%), and adrenal insufficiency (7%) in the nivolumab/ipilimumab group. No treatment-related deaths were reported.
The investigators concluded, “Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory metastatic pancreatic cancer. However, the contribution from SBRT is unknown. Further studies are warranted.”
Inna M. Chen, MD, of the Department of Oncology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and the Danish Comprehensive Cancer Center. For full disclosures of the study authors, visit ascopubs.org.
