ASCO GU 2020: The SEMITEP trial: De-Escalating Chemotherapy in Low-Volume Metastatic Seminoma Based on Early FDG-PET

San Francisco, CA (UroToday.com) Management of patients with good risk metastatic seminoma with etoposide/cisplatin (EP) for 4 cycles is associated with excellent cure rates. However, treatment with EP for 4 cycles may be associated with significant morbidity, including myelosuppression, gastrointestinal toxicity, nephrotoxicity, neurotoxicity, ototoxicity, and death. As such, efforts to minimize the morbidity associated with 4 cycles of EP while maintaining excellent oncologic outcomes are paramount.

To address this issue, Dr. Yohann Loriot and colleagues performed a non-randomized, multiple center, phase II trial (NCT01887340) to assess whether patients with low-volume metastatic seminoma can be treated with 2 cycles of EP followed by only one cycle of carboplatin on the basis of a negative interim fluorodeoxyglucose positron emission tomography (FDG-PET). In the study, all patients who were baseline FDG-PET positive received 2 cycles of EP. After completion of the first 2 cycles, all patients underwent a second FDG-PET to assess response. Patients with a persistently positive FDG-PET proceeded directly to 2 additional cycles of EP (for a total of 4 cycles), while those with a negative FDG-PET received 1 cycle of carboplatin.

The study design is depicted:

ASCO GU 2020 SEMITEP phase II design

The primary outcome was the proportion of patients who were FDG-PET negative on interim imaging and received de-escalating chemotherapy. The secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity.

Of 102 patients enrolled in the study, 99 patients underwent treatment. After the initial 2 cycles of EP, interim FDG-PET was available in 98 patients. One patient died during the initial 2 cycles of EP. Of 71 FDG-PET negative patients, 67 patients proceeded to 1 cycle of carboplatin (carboplatin group). Of 27 FDG-PET positive patients, 31 patients (which included 4 patients who had a negative FDG-PET but requested standard chemotherapy) proceeded to 2 additional cycles of EP (EP group). At a median follow-up of 33.9 months, 12 month PFS rates were 95.4% and 90.0%; 24 month PFS rates were 93.8% and 90.0%; and 36 month PFS rates were 89.9% and 90.0% in the carboplatin and EP groups, respectively. There was a 100% OS rate at 12, 24, and 36 months in the carboplatin and EP groups. With regards to toxicity, patients in the carboplatin group experienced decreased peripheral neuropathy compared to the EP group.

Dr. Loriot concluded that the utilization of de-escalating chemotherapy with 1 additional cycle of carboplatin, compared to standard chemotherapy with 2 additional cycles of EP, after 2 initial cycles of EP appears to be safe and feasible in the majority of patients with low-volume metastatic seminoma. De-escalating chemotherapy also resulted in reduced peripheral neuropathy. Further studies with larger patient cohorts and follow-up are necessary to determine the morbidity profile and long-term oncological efficacy of de-escalating chemotherapy.

Presented by: Yohann Loriot, MD, PhD, Clinician Scientists, Institut Gustave Roussy and University of Paris-Saclay, Villejuif, Paris

Written By: Ziho Lee, MD, Fellow in Advanced Robotic Oncology and Reconstruction, Temple University, Philadelphia, PA, Twitter: @ZLeeGU at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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