No Benefit of Adding Telomerase Peptide Vaccine to Chemotherapy in Patients With Advanced Pancreatic Cancer
In a UK phase III TeloVac trial reported in The Lancet Oncology, Middleton et al found that the sequential or concurrent addition of the telomerase peptide vaccine GV1001 to gemcitabine/capecitabine did not improve survival in patients with locally advanced or metastatic pancreatic cancer.
GV1001 is a human telomerase reverse transcriptase catalytic subunit peptide vaccine that was expected to generate telomerase-specific T-helper cells, activate antigen-presenting cells containing diverse antigens, and prime and activate cytotoxic T cells exhibiting a broad repertoire.
Study Details
In this open-label trial, 1,062 treatment-naive patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma from 51 UK hospitals were randomly assigned starting in March 2007 to gemcitabine/capecitabine alone (n = 358) or together with sequential GV1001 (n = 350) or concurrent GV1001 (n =354).
Chemotherapy alone consisted of six cycles of gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 and capecitabine at 830 mg/m2 twice daily for 21 days every 28 days. Sequential chemoimmunotherapy consisted of two cycles of chemotherapy followed by an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine]) at 75 μg and GV1001 at 0.56 mg on days 1, 3, and 5, once during weeks 2 to 4, and every 6 months thereafter. Concurrent chemoimmunotherapy consisted of six cycles of chemotherapy with GV1001 given as above from the start of chemotherapy with adjuvant GM-CSF. The primary endpoint was overall survival in the intention to treat population.
No Overall Survival Benefit
The trial was terminated somewhat early, in March 2011, due to unfavorable survival in the sequential chemoimmunotherapy group. Median follow-up among surviving patients was 6.0 months. Median overall survival was 7.9 months in the chemotherapy group, 6.9 months in the sequential chemoimmunotherapy group (hazard ratio [HR] = 1.19, P = .05, vs chemotherapy), and 8.4 months in the concurrent chemoimmunotherapy group (HR = 1.05, P = .64, vs chemotherapy).
Median time to disease progression was 6.4 months in the chemotherapy group, 4.5 months in the sequential chemoimmunotherapy group (HR = 1.50, P < .0001, vs chemotherapy), and 6.6 months in the concurrent chemoimmunotherapy group (HR = 1.0, P = .99).
Outcome by Immune Response
Delayed hypersensitivity response assessed in a subgroup of patients occurred in 12% of the sequential chemoimmunotherapy group (n = 154; conditioned on survival to 18 weeks) and 20% of the concurrent group (n = 233; conditioned on survival to 10 weeks). Median overall survival was 7.5 vs 5.8 months (HR = 0.95, P = .85) for patients in the sequential group with vs without response and 9.0 vs 8.0 months (HR = 0.98, P = .90) for those in the concurrent group with vs without response.
T-cell proliferation response assessed in a subgroup of patients occurred in 31% of the sequential group (n = 32) and 15% of the concurrent group (n = 68); 38% and 37% had a total immune response. Median overall survival was 8.4 vs 7.3 months (HR = 0.28, P = .12) from week 18 for patients in the sequential group with vs without total immune response and 10.6 vs 12.2 months (HR = 1.57, P = .27) from week 10 in patients with vs without response in the concurrent group. The pooled hazard ratio for positive total immune response was 1.15 (P = .073).
Adverse Events
The most common grade 3 or 4 adverse events were: neutropenia, occurring in 19% of the chemotherapy group, 17% of the sequential chemoimmunotherapy group, and 22% of the concurrent chemoimmunotherapy group; fatigue, occurring in 8%, 10%, and 12%; and pain, occurring in 9%, 11%, and 12%.
The investigators concluded, “Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy.”
John P. Neoptolemos, MD, of the Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, is the corresponding author for The Lancet Oncology article.
The study was funded by Cancer Research UK and KAEL-GemVax. For full disclosures of the study authors, visit www.thelancet.com.
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®.
