In long-term follow-up of the French phase III GETUG-13 trial reported in the Journal of Clinical Oncology, Fizazi et al reported that intensified chemotherapy was associated with significantly better progression-free survival among patients with poor-prognosis nonseminomatous germ cell tumors with unfavorable decline in tumor markers.
The primary analysis of the trial showed that switching patients with poor-prognosis nonseminomatous germ cell tumors with unfavorable marker decline to intensified chemotherapy resulted in improved outcomes.
Study Details
In the study, 263 patients with poor-prognosis germ cell tumors received one cycle of bleomycin, etoposide, and cisplatin (BEP). Of these, 51 patients with a favorable tumor marker decline received three additional cycles of BEP (Fav-BEP) and 203 with unfavorable marker decline were randomly assigned to three cycles of BEP (Unfav-BEP, n = 98) or a dose-dense chemotherapy regimen consisting of two cycles of paclitaxel-BEP-oxaliplatin plus two cycles of cisplatin, ifosfamide, and bleomycin (Unfav-dose-dense, n = 105).
Key Findings
Median follow-up was 7.1 years (range = 0.3–13.3 year). At 5 years, progression-free survival was 58.9% (95% confidence interval [CI] = 49.3%–67.8%) in the Unfav-dose-dense group vs 46.7% (95% CI = 37.1%–56.5%) in the Unfav-BEP group (hazard ratio [HR] = 0.65, 95% CI = 0.44–0.97, P = .036). More patients in the Unfav-BEP group subsequently received salvage high-dose chemotherapy with stem cell transplantation (17% vs 8%, P = .035). At 5 years, overall survival was 70.9% (95% CI = 61.6%–78.9%) in the Unfav-dose-dense group vs 61.3% (95% CI = 51.3%-70.5%) in the Unfav-BEP group (HR = 0.74, 95% CI = 0.46–1.20, P = .22).
Progression-free survival (HR = 0.53, 95% CI = 0.31–0.89, P = .01) and overall survival (HR = 0.50, 95% = 0.26–0.96, P = .03) were better in the Fav-BEP group vs the Unfav-BEP group.
A total of 3 patients in the Unfav-dose-dense group had grade 3 motor neurotoxicity at 1 year; no grade >1 toxicity was reported after year 2.
The investigators concluded: “Long-term outcomes suggest a sustained benefit of intensified chemotherapy in terms of [progression-free survival] and numerically better survival, with a minimal toxicity and reduced use of salvage high-dose chemotherapy plus stem-cell transplant.”
Karim Fizazi, MD, PhD, Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Institut National du Cancer (Programme Hospitalier de Recherche Clinique), Ligue nationale contre le cancer, CHUGAI, and BAXTER. For full disclosure of all study authors, visit ascopubs.org.
