Orlando, FL—One cycle of the bleomycin, etoposide, and cisplatin (BEP) regimen had less toxicity and was as effective as 2 cycles in patients with high-risk, nonseminomatous or germ-cell tumors of the testis (NSGCTT), according to results of a large prospective trial called 111 presented at the 2017 Genitourinary Cancers Symposium. Using 1 cycle of BEP as standard of care would reduce exposure to toxicity, and most patients with testicular cancer are relatively young.
“This study adds to mounting evidence in favor of 1 cycle of BEP in high-risk patients,” explained lead investigator Robert Huddart, MA, MBBS, PhD, MRCP, FRCR, Leader, Clinical Academic Radiotherapy team, The Institute of Cancer Research, Sutton, England.
“The 111 trial is the biggest formal, prospective trial to date investigating 1 cycle of adjuvant BEP in high-risk, stage 1 NSGCTT. One cycle is safely deliverable, and the 2-year recurrence rate is similar to that seen with 2 cycles of BEP. Adopting 1 cycle as the standard would reduce overall exposure to chemotherapy in this young patient population,” stated Dr Huddart.
There is no standard approach to this patient population, he continued. Some experts favor orchiectomy followed by 2 cycles of BEP.
111 was a single-arm trial that evaluated the use of 1 cycle of BEP as adjuvant chemotherapy in 246 patients with high-risk (defined as lymphovascular invasion), stage 1 NSGCTT from 33 sites in the United Kingdom. More than 20% of patients enrolled in the study were aged >40 years. The median follow-up was 39 months. All patients received prophylaxis with antibiotics and granulocyte-colony stimulating factor. Patients were followed for recurrence (ie, malignant or differentiated teratoma). Malignant recurrences require retreatment with chemotherapy, whereas differentiated teratoma is considered much less aggressive and can be surgically removed.
The majority of acute adverse events associated with 1 cycle of BEP were grade 3 or 4 myelosuppression. Grade 3 or 4 adverse events included neutropenia (32.2%), leukopenia (16.3%), and febrile neutropenia (6.4%). The rates of all nonhematologic toxicities were low.
Delayed toxicity, with ear and labyrinth disorders, was reported in 20% (grade 2) and 1% (grade 3) of patients.
The rate of malignant recurrence was 1.3%, which was well below the 5% target set for the trial. The rate of differentiated teratoma recurrence was 1.3%, and all were completely resected. Thus, the total recurrence rate was 2.6% in the first 2 years of follow-up.
After data cutoff, 1 additional patient had a malignant recurrence, bringing the rate of recurrence to 1.8%.
The recurrence-free rate was 97%, and the overall survival rate at 2 years was 99%.
Pooling the data from the 111 study and 4 other published studies, a total of 16 malignant recurrences were reported in 1004 patients.
“One cycle of BEP reduces the rate of malignant recurrences by 7.5% of the expected level,” Dr Huddart said.
“The study provides robust evidence to inform the decision between adjuvant chemotherapy and intensive surveillance,” he stated.
“Single-cycle treatment is safe and effective and 2 cycles of adjuvant BEP are unnecessary. These findings may alter views of the international community,” said Noel W. Clarke, MBBS, FRCS, ChM, Professor of Urological Oncology, The Christie NHS Foundation Trust, Manchester, England, who was a discussant of this study.
