Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer.

Koichi Takayama,Shunichi Sugawara,Kyogo Itoh,Taishi Harada,Shinzo Takamori,Yasuo Saijo,Tetsuro Sasada,Junji Kishimoto,Atsushi Sato,Akira Yamada,Makoto Maemondo,Yoichi Nakanishi,Tatsuyuki Kakuma,Masanori Noguchi

doi:10.1155/2016/1745108

Abstract

Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m2 on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed.

Highlights

Lung cancer is a leading cause of cancer-related death in Japan
Patients aged 20 years or older with histologically or cytologically confirmed inoperable stage IIIB/IV or recurrent non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild genotype were eligible for enrollment
After excluding 17 ineligible cases because of smaller number of lymphocytes, mutant EGFR genotype, smaller number of neutrophils, and others, remaining 50 patients were randomly assigned to docetaxel plus placebo or docetaxel plus peptide vaccination (PPV) (PPV arm, n = 26)

Summary

Introduction

The treatment with platinum-based chemotherapy improves survival and quality of life (QOL) in patients with advanced non-small-cell lung cancer (NSCLC), a substantial population of patients progress and should be offered second-line treatment [1]. With unsurpassed efficacy compared with other chemotherapeutic regimens, docetaxel alone is the current standard as second-line chemotherapy for advanced NSCLC [2]. With similar PPV treatment, Yoshiyama et al conducted a phase II trial in refractory NSCLC patients recently [7], and forty-one patients were enrolled.

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Conclusion