(UroToday.com) The 2024 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Xin-Gang Bi discussing preliminary results from a phase II trial assessing neoadjuvant combined chemotherapy and immunotherapy for upper tract urothelial carcinoma. Upper tract urothelial carcinoma presents a challenging prognosis even after radical nephroureterectomy, and postoperative renal insufficiency further limits the options for adjuvant therapy. The efficacy of neoadjuvant chemotherapy for upper tract urothelial carcinoma remains uncertain as past studies have not shown satisfactory results and have mostly been retrospective. As such, there is an urgent need for a more promising regimen. This phase II study aimed to investigate the efficacy and safety of a combination of chemotherapy (gemcitabine/cisplatin) and PD-1 inhibitor (toripalimab) as neoadjuvant treatment in upper tract urothelial carcinoma patients.
This trial planned to enroll 34 upper tract urothelial carcinoma patients with either cT1N0M0 (high grade) or cT2-3N0M0, confirmed by ureterorenoscopic biopsy and imaging. The treatment regimen included three or four cycles of neoadjuvant treatment (gemcitabine, 800mg/m2, days 1 and 8/cisplatin, 60mg/m2, day 1/toripalimab, 240mg, day 1 of a 21-day cycle), followed by radical nephroureterectomy and pelvic lymphadenectomy. The primary outcome was the pathological complete response rate, with secondary outcomes including significant downstaging (≤pT1) rate, disease control rate, and safety.
To date, 17 patients have been accrued since August 1, 2020, and recruitment is ongoing. Overall, 15 patients have completed treatments and were preliminarily analyzed, with two patients still undergoing treatment. The median age was 66.0 years, with 53.3% were male. The majority of patients had unifocal tumors, with a median maximum diameter of 2.8 cm (0.4-5.8). All patients experienced obstructed hydronephrosis, and clinical T staging was confirmed by multi-parameter MRI, indicating two T2 and 13 T3 patients. Ureterorenoscopic biopsy revealed 13 high-grade and two low-grade urothelial carcinoma patients, and all patients were classified as high-risk upper tract urothelial carcinoma. Twelve patients completed 4 cycles of neoadjuvant therapy, and three underwent 3 cycles. The median interval time from initiation of neoadjuvant treatment to radical nephroureterectomy and from the end of neoadjuvant treatment to radical nephroureterectomy was 18.3 (11.4-22.7) weeks and 6.3 (0.1-11.6) weeks, respectively. For efficacy outcomes, the pathological complete response rate was 20.0% (3/15), the ≤pT1 rate was 53.3% (8/15), and the disease control rate was 100%. No grade 4-5 chemotherapy-related adverse events were recorded, but 26.7% (4/15) experienced grade 2 myelosuppression, 20% (3/15) grade 3, and 6.7% (1/15) grade 4. Two patients experienced immune-related adverse events after 4 cycles, including hypothyroidism (grade 2) and adrenal insufficiency (grade 2). No surgery-related complications or readmissions within one month were reported, and with a median follow-up of 25.6 months, all patients remained alive and tumor-free.
Dr. Bi concluded this presentation discussing preliminary results from a phase II trial assessing neoadjuvant combined chemotherapy and immunotherapy for upper tract urothelial carcinoma with the following take-home points:
- Preliminary analyses suggest that the combination of chemotherapy and a PD-1 inhibitor as neoadjuvant treatment exhibits a promising pathological complete response rate for upper tract urothelial carcinoma
- The treatment was manageable in terms of safety, with immune-related adverse events potentially leading to prolonged treatment periods
Presented by: Xin-Gang Bi, Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024