Chemotherapy de-escalation feasible in metastatic seminoma
medwireNews: SEMITEP trial results reported at the 2020 Genitourinary Cancers Symposium demonstrate the feasibility of treatment de-escalation based on an interim scan in metastatic seminoma patients with good prognosis.
Addressing the audience in San Francisco, California, USA, the presenter Yohann Loriot (Institut Gustave Roussy, Villejuif, France) noted that one of the key questions in this setting is “how to envision a reduction in treatment burden for reducing significant long-term side-effects of cisplatin-based chemotherapy?”
The SEMITEP investigators postulated that 18F-fluorodeoxyglucose–positron emission tomography (FDG–PET) could help “identify patients with highly chemosensitive disease at an early stage,” thereby sparing the majority from receiving unnecessary treatments.
They enrolled 99 men with treatment-naïve, low-volume, metastatic seminoma with good prognosis as per the International Germ Cell Cancer Collaborative Group classification. Participants were required to have a positive FDG–PET scan at baseline and all men had a second scan after two cycles of treatment with etoposide plus cisplatin. As per the protocol, men with a negative result on the second scan could receive a de-escalated schedule comprising just one cycle of carboplatin, while those with a positive scan would receive the full standard regimen (ie, two more cycles of etoposide–cisplatin).
Of the 98 evaluable participants, 71 had a negative interim FDG–PET scan and 67 went on to receive the de-escalated regimen, with four patients requesting standard chemotherapy. In all, 68.4% of patients were treated with de-escalated chemotherapy, which was higher than the prespecified cutoff of 40.0% and meant that the trial met its primary endpoint.
Loriot commented that the de-escalation strategy yielded “very good results” in terms of progression-free survival over a median follow-up of 33.9 months, with nearly identical 3-year rates of 89.9% and 90.0% in the de-escalated and standard chemotherapy groups, respectively.
He also pointed out that there were no deaths in either group among the evaluable patients, but highlighted that the one unevaluable patient died due to toxicity during the initial two cycles of etoposide–cisplatin.
The rates of nonhematologic adverse events of grade 3 or 4 were low with the de-escalated and standard regimens, said Loriot, and neutropenia was the most common event of this severity in both groups (48% in each group).
Of note, the cumulative incidence of peripheral neuropathy was significantly lower among men who received the de-escalated versus standard regimen, but the rates of ototoxicity and renal dysfunction were comparable and none of the trial participants experienced cardiac or pulmonary toxicity.
“De-escalating chemotherapy based on an early FDG–PET is safe and feasible in metastatic seminoma,” and the SEMITEP trial supports the use of this strategy in these patients, concluded the presenter.
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