Dual-vaccine therapy prolonged survival in pancreatic cancer

SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – Serial administration of two vaccines that stimulate the immune response to pancreatic cancer antigens prolonged survival of metastatic disease by about 2 months, according to Dr. Dung T. Le. A team led by Dr. Le of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore tested the vaccines – GVAX Pancreas and CRS-207 – in 90 patients. The interim results of the phase II trial showed that overall survival was about 4 months with GVAX alone but was 6 months with GVAX followed by CRS-207, Dr. Le reported in a press briefing held before the annual Gastrointestinal Cancers Symposium. The symposium was sponsored by the American Society of Clinical Oncology. In fact, the efficacy data met the criteria for an early halt to the trial, and patients in the single-vaccine arm are now receiving both vaccines. “This is the first randomized study of immunotherapy in metastatic pancreatic cancer demonstrating an improvement in survival,” commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland. “Patients who received at least one dose of the CRS-207 vaccine had a doubling of 1-year survival, and this was accomplished without the side effects of chemotherapy.” Safety results suggested that the vaccines were well tolerated. Local reactions of erythema, warmth, and swelling after intradermal administration of GVAX, as well as transient fevers and chills after infusion of CRS-207, were generally mild and transient. “Additional clinical study of the combination treatment is underway in a three-arm study testing the combination, CRS-207 alone, and chemotherapy alone,” Dr. Le noted. GVAX is an allogeneic whole-cell vaccine. Its genetically modified pancreatic cancer cells secrete granulocyte macrophage colony-stimulating factor, which attracts dendritic cells to the vaccine site, Dr. Le explained. It is given after low-dose cyclophosphamide to inhibit a regulatory T-cell response. CRS-207 consists of live-attenuated Listeria monocytogenes virus vaccine that expresses mesothelin. The vaccine stimulates innate and adaptive immunity to mesothelin, which is highly expressed in pancreatic cancer cells. The investigators tested the vaccines serially in part because GVAX induces a response to a wide variety of tumor-associated antigens, and CRS-207 then boosts the response to mesothelin. Patients in the trial, sponsored by Aduro BioTech, had declined or had experienced a failure of prior chemotherapy. They were randomized 2:1 to receive either two doses of GVAX followed by four doses of CRS-207 or to receive six doses of GVAX therapy alone, with all doses spaced 3 weeks apart. Repeated courses were allowed as long as patients were medically stable. With a median follow-up of 7.8 months, median overall survival among all patients who received at least one dose of vaccine was longer by nearly 2 months with dual-vaccine therapy compared with single-vaccine therapy (6.1 vs. 3.9 months; hazard ratio 0.59; P = .03). The 1-year probability of survival was doubled with dual versus single therapy (24% vs. 12%), according to Dr. Le. In a per-protocol analysis restricted to patients who received at least three doses of vaccine, dual therapy had a greater 5-month overall survival benefit (9.7 vs. 4.6 months; hazard ratio 0.53; P = .03).