Randomized phase II study of docetaxel plus personalized peptide vaccination versus docetaxel plus placebo for patients previously treated for advanced wild-type EGFR non-small-cell lung cancer.

Abstract

e14029 Background: A personalized peptide vaccination (PPV) strategy has been developed as a new immune-system-based therapy. In this method, vaccine antigens are selected and administered based on pre-existing host immunity prior to vaccination. Previous clinical studies on PPV showed promising results for treating various types of advanced cancers, including lung cancer. However, the clinical efficacy of PPV in combination with standard chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains unclear. We therefore conducted this multicenter, randomized, phase II trial. Methods: Fifty previously treated PS0-1 patients with stage IIIB/IV EGFR wild-type NSCLC were randomly assigned to the docetaxel (60 mg/m2on day 1) plus PPV arm based on pre-existing host immunity (n = 24) or to the docetaxel plus placebo arm (n = 26). Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly during the first 8 weeks and biweekly during the subsequent 16 weeks. The first PPV or placebo injection was performed within 3 days of docetaxel administration. The primary efficacy endpoint was progression free survival. Results: The toxicity profile of docetaxel plus PPV was very similar to that previously reported for docetaxel alone. PPV-related toxicity was grade 1 or 2 skin reaction. The median PFS was 53 days in the placebo arm and 59 days in the PPV arm. There was no significant difference between the arms by the log-rank test (p = 0.42). Interestingly, PFS and overall survival in humoral immunological responders were significantly longer than in non-responders, with hazard ratio 0.28 and 0.27 (both p < 0.01), respectively. Conclusions: The primary endpoint was not met in this clinical trial and PPV did not improve survival when combined with docetaxel for previously treated advanced EGFR wild-type NSCLC. However, PPV may be efficacious for humoral immunological responders. Further clinical investigation is needed to identify which patients will benefit from cancer vaccination. Clinical trial information: 000003521.