Intensified Chemotherapy Based on Tumor Marker Decline May Improve Progression-Free Survival in Patients With Poor-Prognosis Germ Cell Tumors
In the phase III GETUG 13 trial reported in The Lancet Oncology, Fizazi et al found that treatment intensification based on early tumor marker decline resulted in a numeric and borderline statistically significant improvement in progression-free survival in patients with poor-prognosis germ cell tumors.
Study Details
The trial included 254 patients with testicular, retroperitoneal, or mediastinal nonseminomatous germ cell tumors and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations who were enrolled between November 2003 and May 2012 in 20 French centers, 1 U.S. center, and 1 Slovakian center. After one cycle of cisplatin, etoposide, and bleomycin (BEP), human chorionic gonadotropin and alfa-fetoprotein concentrations were measured on day 18 to 21.
Patients with a favorable decline in tumor markers received BEP for three additional cycles (favorable-BEP group; n = 51); patients with an unfavorable decline were randomly assigned to receive three additional cycles of BEP (unfavorable-BEP group; n = 98) or a dose-dense regimen (unfavorable dose-dense group; n = 105) consisting of paclitaxel before BEP plus oxaliplatin, cisplatin, ifosfamide, mesna, and bleomycin with granulocyte-colony stimulating factor support. The primary endpoint was progression-free survival in the intent-to-treat population. Follow-up is ongoing.
Progression-Free Survival Outcomes
Median follow-up was 4.1 years. Three-year progression-free survival was 70% (95% confidence interval [CI] = 57%–81%) in the favorable-BEP group (hazard ratio [HR] = 0.66, P = .01, vs unfavorable-BEP group), 59% (95% CI = 49%–68%) in the unfavorable dose-dense group (HR = 0.66, P = .05, vs unfavorable-BEP group), and 48% (95% CI = 38%–59%) in the unfavorable-BEP group.
Three-year overall survival was 84% (95% CI = 71%–92%) in the favorable-BEP group, 73% (95% CI = 64%–81%) in the unfavorable dose-dense group (HR = 0.78, P = .34, vs unfavorable-BEP group), and 65% (95% CI = 55%–75%) in the unfavorable-BEP group.
Toxicity
Compared with patients in the unfavorable-BEP group, those in the dose-dense group had more grade 3 or 4 neurotoxic events (7% vs 1%) and hematologic adverse events, including anemia (44% vs 26%) and thrombocytopenia (31% vs 16%); rates of grade 3 or 4 neutropenia (60% vs 63%) and grade 1 or 2 febrile neutropenia (17% vs 18%, no higher grade cases) were similar in the 2 groups. Toxic death occurred in 1% of patients in each group. Salvage high-dose chemotherapy plus stem cell transplantation was required in 6% vs 16% of patients.
The investigators concluded: “Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline.”
Karim Fizazi, MD, of Institut Gustave Roussy, is the corresponding author for The Lancet Oncology article.
The study was funded by the Institut National du Cancer. For full disclosures of the study authors, visit www.thelancet.com.
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