A study reports long-term results from the CCTG PA.7 phase II trial testing whether adding immunotherapy to chemotherapy improves outcomes for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The trial evaluated the combination of durvalumab and tremelimumab with standard chemotherapy (gemcitabine and nab-paclitaxel). Overall, the addition of immunotherapy did not significantly improve survival in the general patient population. Median overall survival was 9.84 months with the combination therapy compared with 8.76 months for chemotherapy alone, while progression-free survival was nearly identical at about 5.4 months in both groups.
Despite the limited benefit overall, researchers observed a small group of long-term survivors. About 3.3% of patients lived longer than four years, and the five-year survival rate was 3.48% in the immunotherapy group compared with 1.67% in the chemotherapy-only group. Investigators used circulating tumor DNA (ctDNA) sequencing to understand why some patients responded better than others.
The analysis identified a biomarker linked to mutations in four DNA damage repair genes—BRCA1, POLE, ATM, and FANCA. Around 10% of patients carried at least two mutations across these genes. In the immunotherapy group, these patients had much better outcomes, with a median overall survival of 26.16 months and progression-free survival of 14.59 months, along with a response rate of 63.6%. The survival advantage was not seen in patients treated with chemotherapy alone, suggesting that this DNA repair mutation signature may help identify pancreatic cancer patients more likely to benefit from immunotherapy.