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Early FDG-PET Allows De-escalation of Chemotherapy in Metastatic Seminoma


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In patients with metastatic seminoma, the early use of 18F-fluorodeoxyglucose (FDG)–positron-emission tomography (PET) to risk-stratify patients enabled the de-escalation of chemotherapy, avoiding treatment with bleomycin—one of the most toxic drugs used to treat this cancer—and excessive doses of etoposide and cisplatin.

In the SEMITEP study, more than 90% of patients were alive without disease progression at 3 years after a negative midtreatment PET scan, followed by half as much additional treatment as they would have been subjected to without FDG-PET risk stratification. Among all patients enrolled in the trial, 72% had negative midtreatment PET scans after two cycles of etoposide and a platinum agent (EP). These results were presented at the 2020 Genitourinary Cancers Symposium.1

Yohann ­Loriot, MD

Yohann ­Loriot, MD

“De-escalation of chemotherapy based on early FDG-PET is safe and feasible in metastatic seminoma,” said lead author Yohann ­Loriot, MD, of Gustave Roussy Institute, Villejuif, France. “The de-escalation strategy provides for shorter treatment and less neuropathy. And it avoids the use of bleomycin and its associated toxicity. The SEMITEP trial supports the de-escalating strategy in metastatic seminoma and should be adopted in clinical practice,” he stated.

SEMITEP Background

As background, Dr. Loriot explained that metastatic seminoma is a rare tumor with cure rates ranging from 80% to 90%, depending on risk category. Patients with stage IIA disease are treated with radiation; patients with stage IIB disease are treated with radiation or chemotherapy, and those with stages IIC and III disease are treated with chemotherapy.

Traditional chemotherapy for favorable-risk seminoma is three cycles of bleomycin, etoposide, and cisplatin. “Recent studies have suggested that four cycles of EP can lead to cure in good-risk patients with metastatic seminoma, with a 3-year overall survival rate of 99%,” he said.

Guidelines recommend FDG-PET in metastatic seminoma tumors greater than 3 cm. This imaging modality has a high negative predictive value and a low positive predictive value approaching 20%.

Study Details

The SEMITEP study evaluated a risk-adapted strategy based on interim FDG-PET imaging, with the goal of sparing patients unnecessary treatment and associated toxicity. “Our working hypothesis was that FDG-PET may identify highly chemosensitive disease at an early stage,” Dr. Loriot told listeners.

The study enrolled 102 patients from 17 different clinics with PET-positive, good-prognosis, metastatic seminoma (stage IIB–III), and no prior chemotherapy or radiation therapy. Patients were treated with two cycles of EP followed by FDG-PET imaging. Patients with PET-positive scans were treated with an addition two cycles of EP, and those with PET-negative scans were treated with one cycle of carboplatin (de-escalated arm). For the purposes the of the study, a positive FDG-PET scan was defined as abnormal focal uptake of FDG with or without anatomic abnormalities detected by CT scanning.

The primary endpoint was the percentage of patients with negative midtreatment FDG-PET treated with de-escalated therapy. Ninety-eight patients were evaluated for efficacy. The mean age was 40 years. Two-thirds of patients had stage IIB disease, and 95% had primary testicular cancer.

Negative midtreatment PET scans were reported in 71 of 98 patients. Four of these patients requested standard therapy, which was an additional two cycles of EP. The remining 67 patients received one cycle of carboplatin.

At a median follow-up of 33.9 months, progression-free survival rates in the de-escalated arm were 95.4% at 12 months, 93.8% at 24 months, and 89.9% at 36 months. Corresponding progression-free survival rates in the standard therapy arm were 90% at all three timepoints. The 3-year overall survival was 100% for all patients enrolled in the trial. Nine patients had disease progression, mainly in the retroperitoneal area. No deaths were reported in either study arm.

“Very few grade 3 toxicities were reported,” Dr. Loriot said. “They mainly included anemia [16%], nausea/vomiting [3%], neutropenia [48%], and thrombocytopenia [10%].” More than half of the patients in the standard arm developed peripheral neuropathy, compared with few in the de-escalated arm. Ototoxicity occurred in 30% of the standard arm and about 20% of the de-escalated arm. 

DISCLOSURE: The study was supported by the French National Cancer Institute. Dr. Loriot has received honoraria from Pfizer and Sanofi; has served in a consulting or advisory role for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Janssen, MSD Oncology, Roche, and Seattle Genetics; has received institutional research funding from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, CureVac, Exelixis, Incyte, Janssen Oncology, Medivation, MSD Oncology, Nektar, Oncogenex, Pfizer, and Sanofi; and has been reimbursed for travel, accommodations, or other expenses by Astellas Pharma, AstraZeneca, Janssen Oncology, MSD Oncology, Roche, and Seattle Genetics.

REFERENCE

1. Loriot Y, Texier M, Culine S, et al: The SEMITEP trial: De-escalating chemotherapy in low-volume metastatic seminoma based on early FDG-PET. 2020 Genitourinary Cancers Symposium. Abstract 387. Presented February 14, 2020.

 


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