Seminoma: Risk-Adapted Strategy Could Mean Less Toxic Chemo

Susan London

February 24, 2020

SAN FRANCISCO ― Use of FDG-PET early in the course of chemotherapy can identify men with low-volume seminoma who have highly chemosensitive disease, enabling them to safely skip the standard chemotherapy regimen with its toxicity. This was among key findings of the phase 2 SEMITEP trial reported at the 2020 Genitourinary Cancers Symposium. Although four cycles of etoposide-cisplatin cure almost all cases of good-prognosis metastatic seminoma (Eur Urol. 2014;65:381-6), long-term cisplatin toxicity in this predominantly young population remains problematic, noted lead investigator Yohann Loriot, MD, PhD, a medical oncologist at Gustave Roussy Institute, Villejuif, France.

In SEMITEP, he and his colleagues tested a risk-adapted strategy among 98 patients with metastatic seminoma who met International Germ Cell Cancer Collaboration Group criteria for good prognosis and had not received any chemotherapy or radiotherapy.

Fully 68.4% had a negative FDG-PET result after two cycles of etoposide-cisplatin and were given only one cycle of carboplatin to complete treatment (based on that drug's activity in low-volume disease), Dr. Loriot reported. The rest went on to receive an additional two cycles of etoposide-cisplatin, completing the standard regimen.

At 3 years, 9 in 10 patients were alive and free of progression in both the deescalated chemotherapy group and the standard chemotherapy group. The cumulative incidence of peripheral neuropathy, however, was about 10 times higher in the latter.

"Deescalating chemotherapy based on an early FDG-PET is safe and feasible in metastatic seminoma. This strategy provides shorter treatment, reduces neuropathy, and eliminates need for bleomycin and its associated toxicity," Dr. Loriot concluded. "SEMITEP supports the deescalating strategy in metastatic seminoma."

Ready for Prime Time?

The SEMITEP trial achieved the main goal of reducing toxicity but had several noteworthy caveats, according to invited discussant Peter Albers, MD, professor and chairman of the department of urology, Heinrich-Heine University Düsseldorf, Germany.

First, in an "astonishing" feat, FDG-PET was performed and evaluable after just two cycles of chemotherapy, or 3 weeks, when typical practice is to wait until 8 or 10 weeks, he said.

"Second, I really don't understand why carboplatin was given in an FDG-PET–negative seminoma. There is, in my view, no reason to add another chemotherapy agent to this patient population if you really claim this to be a biomarker," he said. "Carboplatin is known to be inferior to cisplatin in metastatic seminoma."

Third, enrolled patients predominantly had low-volume disease, with about two-thirds having clinical stage IIA or IIB. "So this study is not representative for all metastatic seminoma patients," Dr. Albers cautioned. "But obviously, it gives a good signal, and those patients who had IIC disease in the deescalation arm have shown no recurrences so far.

"This trial is important and obviously accurately done, but to my mind, it's not yet practice-changing. We need a clear comparison to standard treatment before we introduce FDG-PET as a biomarker in this indication," he concluded, recommending that for now, risk-stratified approaches should be limited to clinical trials.

Study Details

Although 72% of patients in SEMITEP had a negative early FDG-PET result, four of them requested standard chemotherapy anyway and were analyzed in that group, Dr. Loriot noted at the symposium, which was sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

With a median follow-up of 33.9 months, the 36-month rate of progression-free survival was 89.9% in the deescalated chemotherapy group, essentially the same as the 90% in the standard chemotherapy group. There were no deaths during follow-up in either group.

During chemotherapy, the deescalation group had lower rates of grade 3 or 4 nausea and vomiting and ototoxicity, and a higher rate of grade 3 or 4 thrombocytopenia.

At 3 years, the cumulative incidence of any-grade peripheral neuropathy was less than 5% in the deescalated chemotherapy group, compared with about 50% in the standard chemotherapy group (P less than .001). There was also a trend toward a lower incidence of ototoxicity with deescalation.

Dr. Loriot disclosed no relevant conflicts of interest. The trial was funded by Institut National du Cancer (Programme Hospitalier de Recherche Clinique). Dr. Albers disclosed honoraria from Sanofi and a consulting or advisory role with MSD, Roche, and Sanofi.

SOURCE: Loriot Y et al. GUCS 2020. Abstract 387.

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