De-escalating Chemotherapy Possible in Low-Risk Patients with Advanced Testicular Cancer

April 2020, Vol 11, No 2

San Francisco, CA—De-escalating chemotherapy based on a negative positron- emission tomography (PET) scan after 2 cycles of treatment is safe and feasible in most patients with low-volume metastatic seminoma, the most common type of testicular cancer, according to results presented at the 2020 Genitourinary Cancers Symposium.

In a multicenter phase 2 study of patients with low-volume metastatic seminoma with good prognosis, 72% of patients had a negative fluorodeoxyglucose (FDG)-PET after 2 cycles of etoposide plus cisplatin chemotherapy, and could safely de-escalate treatment.

“De-escalating chemotherapy based on early FDG-PET is safe and feasible in metastatic seminoma,” said Yohann Loriot, MD, PhD, Oncologist, Urology Committee, Testicular Cancer, Gustave Roussy, Villejuif, France, and lead investigator of the SEMITEP trial.

“This strategy provides shorter treatment, reduced neuropathy, and no need for bleomycin and its associated toxicity,” he said.

SEMITEP Trial Details

The SEMITEP trial investigated a therapeutic strategy guided by FDG-PET in patients with seminoma in 2 cohorts. The first cohort consisted of patients with nonmetastatic (stage I) seminoma, for whom results were reported in 2018. The data presented at the symposium were from a cohort of patients with metastatic seminoma, a rare tumor that predominantly affects young men. Prognosis is generally excellent, with cure rates of 80% to 90%, depending on the prognostic category.

Good-risk patients are characterized by the absence of nonpulmonary visceral metastases. The current management strategy for good-risk patients is radiotherapy for patients with stage IIA disease, radiotherapy or chemotherapy for stage IIB, and chemotherapy for stage IIC and stage III disease. The 2 accepted chemotherapy regimens are 3 cycles of bleomycin, etoposide, and cisplatin, or 4 cycles of etoposide plus cisplatin. In the event of residual masses >3 cm, FDG-PET is recommended to evaluate the need for surgery.

A negative FDG-PET predicts the absence of viable seminoma cells after chemotherapy. “FDG-PET provides a high negative predictive value [approximately 90%] but a low positive predictive value in predicting viable tumor cells,” said Dr Loriot. “So FDG-PET may spare the majority of patients unnecessary treatments to prevent side effects, particularly long-term toxicities.”

The SEMITEP study aimed to develop a risk-adapted strategy to spare patients excessive treatments, with a working hypothesis that FDG-PET may identify patients with highly chemosensitive disease at an early stage.

The patients enrolled in the study had stage IIB, IIC, or III metastatic seminoma with good prognosis, based on the International Germ Cell Consensus Classification. Patients could not have received previous chemotherapy or radiotherapy. After 2 cycles of etoposide plus cisplatin, FDG-PET was performed on day 17 to day 20 of cycle 2. If the early FDG-PET findings were positive (defined as the presence of an abnormal focal uptake of FDG regardless of anatomic alterations in the corresponding CT image), patients received standard chemotherapy. If the FDG-PET finding was negative, patients had chemotherapy de-escalated to 1 cycle of carboplatin.

The primary study end point was the proportion of patients with a negative early FDG-PET who received de-escalating chemotherapy.

A total of 102 patients were enrolled, 64% with clinical stage IIB tumors. The testis was the primary tumor site in 95% of patients. A total of 3 patients were not evaluable, and 1 patient died from adverse events before early FDG-PET, leaving a total of 98 evaluable patients.

SEMITEP Study Results

A total of 71 patients had a negative early FDG-PET result and 27 patients had a positive result. Four patients with a negative FDG-PET result requested standard chemotherapy, and 67 (68.4%) patients received de-escalating chemotherapy (the primary end point).

“This strategy yielded very good results in terms of progression-free survival [PFS],” said Dr Loriot. “The median follow-up was 33.9 months, and at 3 years, the PFS rate of patients treated with 4 cycles of EP [etoposide plus cisplatin] was 90%, and is identical to the patients treated with 2 cycles of EP and 1 cycle of carboplatin.”

Overall, 9 patients overall had disease progression, 7 of which were in the retroperitoneum. No deaths occurred in patients receiving etoposide plus cisplatin or carboplatin.

During chemotherapy, grade 3 or 4 nonhematologic toxicity was rare. The most frequent toxicities in both groups were neutropenia (48%) and anemia (16%). A significantly higher proportion of patients who received 4 cycles of etoposide plus cisplatin had peripheral neuropathy. No significant difference was seen between the groups in the rates of ototoxicity or renal dysfunction, and no patient had cardiac or pulmonary toxicities.

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