De-escalation chemotherapy after negative PET scan appears safe in low-volume metastatic seminoma
Click Here to Manage Email Alerts
De-escalation of treatment after two cycles of chemotherapy and a negative PET scan appeared safe and feasible among a cohort of men with low-volume metastatic seminoma, according to results of a phase 2 trial presented at Genitourinary Cancers Symposium.
“A negative FDG-[PET] predicts the absence of viable seminoma cells after chemotherapy in men with metastatic seminoma,” Yohann Loriot, MD, PhD, oncologist in the department of cancer medicine at Institut Gustave Roussy in Villejuif, France, and colleagues wrote.
“In this study, we assessed whether patients with low-volume metastatic seminoma can be treated with two cycles of etoposide [plus] cisplatin followed by only one cycle of carboplatin on the basis of a negative interim PET scan, thereby limiting the burden of toxicity,” they added.
The multicenter, phase 2 trial included 99 men with good-prognosis, low-volume, metastatic seminoma and baseline positive PET scans.
All men received two cycles of etoposide plus cisplatin followed by a second PET scan to assess treatment response. Men with a second positive PET scan proceeded directly to the standard regimen of two additional cycles of etoposide plus cisplatin. Men with a negative PET scan received only one cycle of carboplatin.
The proportion of men with an interim PET-negative scan who received de-escalating chemotherapy served as the primary endpoint. PFS and OS served as secondary endpoints.
After the first two cycles of etoposide plus cisplatin, 94 men had available PET scans. Sixty-seven percent (95% CI, 57.5-76.5) of men had a negative interim PET scan and went on to receive one cycle of carboplatin, whereas 25.5% (95% CI, 17.1-34.9) of men who had a positive interim PET scan received an additional two cycles of etoposide plus cisplatin.
At median follow-up of 34.4 months, two men in the etoposide-cisplatin group and six men in the carboplatin-only group relapsed.
Two-year PFS was 93.7% (95% CI, 84.9-97.5) in the carboplatin group vs. 92.9% (95% CI, 77.4-98) in the etoposide-cisplatin group.
One patient death occurred during the first two cycles of treatment, according to the researchers. – by Jennifer Southall
Reference:
Loriot Y, et al. Abstract 387. Presented at: Genitourinary Cancers Symposium; Feb. 13-15, 2020; San Francisco.
Disclosures: The study was funded by Institut National du Cancer (Programme Hospitalier de Recherche Clinique). Loriot reports honoraria from Pfizer and Sanofi; consultant/advisory roles with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Janssen, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics; research funding to his institution from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, CureVac, Exelixis, Incyte, Janssen Oncology, Medivation, Merck Sharp & Dohme Oncology, Nektar, Oncogenex, Pfizer and Sanofi; and travel accommodations/expenses from Astellas Pharma, AstraZeneca, Janssen Oncology, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to Top
Yung Lyou, MD, PhD
Good-risk metastatic seminoma has an excellent rate of cure or chronic remission with the current chemotherapy regimen that combines etoposide and cisplatin for four cycles. However, this chemotherapy regimen is accompanied by toxicities, such as myelosuppression, kidney injury, peripheral neuropathy and hearing loss. Because of this, there has been investigation to de-escalate this intense chemotherapy regimen to an alternative with lower toxicities while still maintaining the same efficacy.
Analysis of the results showed men in both groups achieved similar PFS, and those in the de-escalation group experienced fewer toxicities. This suggests that de-escalation is a viable strategy for patients who achieve chronic remission after two cycles of etoposide chemotherapy, and patients may be able to safely receive one additional cycle of single-agent carboplatin treatment and reduce their overall chemotherapy-related toxicities.
The main limitation of this trial is the sample size. The data need to be verified in a larger phase 3 clinical trial. If the results of that larger trial were comparable to the results of this phase 2 trial, then this would be a paradigm-shifting strategy that would change the standard of care for patients with good-risk metastatic seminoma who may be able to receive this de-escalated approach and, thus, potentially experience much fewer toxicities and improved quality of life.
Click Here to Manage Email Alerts