The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).
In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled.
Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8 and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ypT1), disease-free survival (DFS) and safety.
Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well-tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical CR (cCR) was achieved in 59% of ITT population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative PD-L1 did not correlate with pCR or pathologic downstaging rates.
Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41;CRIS.nih.go.kr,KCT0003804).
Cancer research and treatment. 2022 Oct 06 [Epub ahead of print]
Hongsik Kim, Byong Chang Jeong, Joohyun Hong, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Wan Song, Hyun Hwan Sung, Jung Yong Hong, Se Hoon Park
Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/36228654