SBRT Plus Nivolumab/Ipilimumab Yields Meaningful Activity in Metastatic Pancreatic Cancer

Results from the phase 2 CheckPAC trial indicated that stereotactic body radiotherapy plus nivolumab and ipilimumab produced a promising clinical benefit rate for patients with refractory metastatic pancreatic cancer.

Treatment with stereotactic body radiotherapy (SBRT) plus nivolumab (Opdivo) and ipilimumab (Yervoy) demonstrated clinically meaningful antitumor activity and a favorable safety profile in patients with refractory metastatic pancreatic cancer, according to data from the phase 2 CheckPACtrial (NCT02866383) published in the Journal of Clinical Oncology.

In patients who received SBRT plus nivolumab, the clinical benefit rate was 17.1% (95% CI, 8.0%-30.6%) vs 37.2% (95% CI, 24.0%-52.1%) for those who received SBRT, nivolumab, and ipilimumab. A partial response was seen in 1 patient in the doublet cohort that lasted 4.6 months compared with 6 patients in the triplet regimen arm who had a median duration of response of 5.4 months (95% CI, 4.2-not reached); 1 patient had a response lasting 55 months after inclusion and was still alive.

A total of 84 patients were included in the analysis, including 41 in the SBRT/nivolumab group and 43 in the triplet arm. A total of 83 patients had known mismatch repair (MMR) status and were MMR proficient. Patients in arm A were treated with SBRT at 15 Gy on day 1 and 3 mg/kg of nivolumab administered intravenously on day 1 and once every 2 weeks. Those in arm B received the same regimen plus the addition of 1 mg/kg of intravenous ipilimumab on day 1 every 6 weeks.

Eighty deaths occurred and the median follow-up was 4.1 months (95% CI, 3.7-5.8). Among patients who received SBRT, liver metastases were the most radiated target (77.4%). Nivolumab was given at a median number of 4 cycles in both arms, while the median number of ipilimumab cycles in arm B was 2. In each arm, there was 1 patient who completed a year of treatment, and in arm B, 2 patients were reintroduced to the triplet regimen.

In the triplet arm, the median progression-free survival (PFS) was 1.6 months (95% CI, 1.6-2.8) compared with 1.7 months (95% CI, 1.6-1.8) in the doublet arm. Moreover, the median overall survival (OS) was 3.8 months (95% CI, 2.8-6.5) vs 3.8 months (95% CI, 3.1-5.8) in the doublet and triplet arms, respectively. In arm B, the objective response rate was 14.0% (95% CI, 6.0%-26.5%) compared with 2.4% (95% CI, 0.3%-10.8%) in arm A.

Subsequent treatment was necessary in 5 patients with progressive disease. One patient achieved stable disease for 12 months, although no other long-lasting responses were reported following next therapy. Post-progression therapy was given to 9 patients. In 1 patient who received gemcitabine/nab-paclitaxel, a durable response by RET kinase inhibitor was observed.

During the trial, there were no treatment-related deaths. Grade 3/4 treatment-related adverse effects (TRAEs) occurred In 24.4% of patients in arm A, with the most common being fatigue in 9.8%. In arm B, 30.2% of patients had grade 3/4, the most common of which were diarrhea (11.6%), fatigue (9.3%), adrenal insufficiency (7.0%), colitis (4.7%), arthralgia (4.7%), myalgia (4.7%), and increased serum aspartate aminotransferase levels (4.7%). Treatment discontinuation occurred in 3 patients in arm B because of TRAEs, with 1 patient discontinuing because of grade 4 cardiac arrest.

PD-L1 expression was observed in 24.5% of patients at baseline and 47.6% on treatment. PD-L1 positivity by combined positive score was identified in 48.9% of patients at baseline and 69.0% were confirmed via on-treatment biopsy. Tumor proportion score and combined positive scores of 1% or greater were not associated with clinical benefit or durable survival. At cutoffs of 5%, 10%, and 50% for tumor proportion score and combined positive score, there was no difference in clinical outcomes observed. Investigators did not find a difference in cytokine levels in patients with or without clinical benefits at baseline.

Reference

Chen IM, Johansen JS, Theile S, et al. Randomized phase II study of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy for refractory metastatic pancreatic cancer (CheckPAC). J Clin Oncol. 2022;40(27):3180-3189. doi:10.1200/JCO.21.02511