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Prime-Boost Vaccine Increases Survival in Metastatic Pancreas Cancer

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Key Points

  • Prime-boost vaccination with GVAX and CRS-207 was associated with longer overall survival compared with GVAX alone.
  • Vaccination was well tolerated.

In a study reported in the Journal of Clinical Oncology, Le et al found that adding Listeria monocytogenes–expressing mesothelin (CRS-207) boost to GVAX pancreas vaccine priming resulted in improved overall survival in patients with previously treated metastatic pancreas adenocarcinoma.

Study Details

The GVAX pancreas vaccine, which consists of granulocyte-macrophage colony-stimulating factor–secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is given with low-dose cyclophosphamide to inhibit regulatory T cells. CRS-207, which consists of live-attenuated L monocytogenes–expressing mesothelin, induces innate and adaptive immunity.

In the study, 90 patients with metastatic disease were randomly assigned 2:1 to two doses of cyclophosphamide/GVAX followed by four doses of CRS-207 (n = 61) or six doses of cyclophosphamide/GVAX (n = 29) every 3 weeks. Patients with stable disease could receive additional courses. The primary endpoint was overall survival. In total, 97% of patients had received prior chemotherapy and 51% had received at least two regimens for metastatic disease.

Overall Survival

Mean number of doses given was 5.5 in the prime-boost group and 3.7 in the GVAX-alone group. Median overall survival was 6.1 vs 3.9 months (hazard ratio [HR] = 0.59, P = .02). In a prespecified per-protocol analysis among patients who received at least three doses (two of cyclophosphamide/GVAX plus one of CRS-207 or three of cyclophosphamide/GVAX), median overall survival was 9.7 vs 4.6 months (HR = 0.53, P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer overall survival irrespective of treatment.

Toxicity

The most common treatment-related grade 3 or 4 adverse events in the prime-boost group were lymphopenia (8.2% vs 3.4%), increased AST (4.9% vs 0%), fatigue (4.9% vs 0%), and pyrexia (4.9% vs 0%). The most common in the GVAX group in addition to lymphopenia were anemia (3.4% vs 0%), abdominal pain (3.4% vs 1.6%), and vaccination site pain (3.4% vs 1.6%).

The investigators concluded: “Heterologous prime/boost with [cyclophosphamide]/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity.”

Dung T. Le, MD, of Sidney Kimmel Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Aduro BioTech and grants from the National Institutes of Health. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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