In a French phase II trial (iNDUCT-GETUG V08) reported in the Journal of Clinical Oncology, Houédé et al found evidence of activity of neoadjuvant durvalumab plus chemotherapy in patients with high-risk, upper-tract urothelial carcinoma.
Study Details
In this multicenter open-label trial, 45 evaluable patients, enrolled between 2021 and 2024, received neoadjuvant therapy with durvalumab at 1,500 mg on day 1 and gemcitabine at 1,000 mg/m2 on day 1 and day 8 along with either (depending on estimated glomerular filtration rate) cisplatin at 70 mg/m2 on day 1 or carboplatin AUC = 4.5 on day 1 every 3 weeks for four cycles, followed by radical nephroureterectomy. The primary outcome measure was pathologic complete response (ypT0) rate, with an efficacy threshold level of at least 25%.
Key Findings
A total of five patients switched to carboplatin during treatment.
Rates of pT0 at surgery were 14% (4 of 29 patients) in the cisplatin cohort and 5% (1 of 19 patients) in the carboplatin cohort. The efficacy threshold was not met in either cohort. Rates of pTa/pT1 were 52% (15 of 29 patients) in the cisplatin cohort and 42% (8 of 19 patients) in the carboplatin cohort.
No severe immune-mediated toxicity was observed. Grade 3 or 4 treatment-related toxicity included neutropenia in five patients (grade 3 in four, grade 4 in one), thrombocytopenia in two patients (grade 3 in one, grade 4 in one), and anemia in three patients (all grade 3).
The investigators concluded: “Although our negative study did not meet its primary endpoint in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good, and the surgical risk was not increased.”
Nadine Houédé, MD, PhD, of the Department of Oncology, CHU Nîmes, France, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
