Emerging Therapies and Novel Targets in Pancreatic Cancer

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The investigation of immunotherapy has shown promise across a variety of malignancies, including pancreatic cancer. One promising approach being developed by NewLink Genetics is the HyperAcute immunotherapy algenpantucel-L, notes E. Gabriela Chiorean, MD. This vaccine is engineered through the genetic modification of two pancreatic cancer cell lines to express alpha-gal, which is a foreign carbohydrate to humans that causes an immune reaction.

In a phase II study presented at the 2013 ASCO Annual Meeting, algenpantucel-L was explored in combination with 5-FU and gemcitabine plus radiation therapy for patients with resected pancreatic cancer. Increased antimesothelin antibody levels correlated with more than a doubling in overall survival (OS), notes Chiorean. The median OS was 42 months with the vaccine compared with 20 months for the chemoradiotherapy alone.

The phase III PILLAR study has been formed to assess the effectiveness of algenpantucel-L in patients with locally advanced unresectable pancreatic cancer, notes Chiorean. In this study, the vaccine will be combined with FOLFIRINOX or gemcitabine plus paclitaxel. Following this treatment, patients who progress will receive salvage chemotherapy plus or minus the vaccine. Those who do not progress will receive chemoradiation with or without algenpantucel-L.

In addition to immunotherapy, new studies are exploring the treatment of patients with BRCA1/2 mutations, which were characterized in a study that examined Jewish patients with pancreatic adenocarcinoma, notes Francis P. Arena, MD. Overall, this analysis found that 5.5% of Ashkenazi patients had a BRCA1/2 mutation. Moreover, a correlation between BRCA2 mutations and increased risk for pancreatic cancer was identified. These mutations could help explain why younger patients develop pancreatic cancer, believes Arena.

Studies exploring the treatment of BRCA1/2-mutated patients with pancreatic cancer using PARP inhibitors are currently under way. One study is exploring treatment with gemcitabine and cisplatin with or without veliparib or veliparib monotherapy in patients with BRCA or PALB2-mutated pancreatic cancer.

The assessment of response for patients with pancreatic cancer may also be enhanced in coming years, notes moderator Johanna Bendell, MD. In an analysis of the phase III MPACT study, metabolic response using PET was compared with tumor response by CT for patients with metastatic pancreatic cancer. The rate of response was doubled using PET compared with CT, notes Ramesh K. Ramanathan, MD. Patients with a response by PET had better long-term outcomes compared with CT. This analysis suggests that PET scans could be utilized shortly after administering treatment in order to gauge response.