(UroToday.com) The 2023 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Marc-Oliver Grimm discussing the final results of TITAN-TCC in metastatic urothelial carcinoma. Nivolumab is approved in second line metastatic urothelial carcinoma after platinum-based chemotherapy.1
Additionally, studies suggest improved outcomes for dual checkpoint inhibition in particular with high doses of ipilimumab (nivolumab 1 mg/kg + ipilimumab 3 mg/kg). At the 2023 ESMO annual congress, Dr. Grimm and colleagues reported final data of TITAN-TCC trial that used a tailored approach with nivolumab and nivolumab + ipilimumab boosts for non-responders.
This was a phase II trial with recruitment at 26 sites in Germany and Austria between August 8, 2017, to February 18, 2021. Patients with metastatic urothelial carcinoma started nivolumab induction (240 mg every 2 weeks x4 treatments). Non-responders of cohorts 1 (dose escalation) and 2 (high dose ipilimumab) received nivolumab + ipilimumab boosts. Responders to nivolumab induction continued with nivolumab maintenance (240mg every 2 weeks) but could receive nivolumab + ipilimumab per the respective schedules for later progression. Repeated boost phases were possible. The trial design is as follows:
The primary endpoint for this trial was objective response rate (ORR) to nivolumab ± nivolumab + ipilimumab per RECIST1.1, and secondary endpoints included ORR to nivolumab induction, progression-free survival (PFS), and overall survival (OS).
In cohort 1, 42 patients were first line and 44 second/third line; cohort 2 recruited second/third line patients only with 83 being enrolled. The baseline characteristics are as follows:
The ORR to nivolumab induction was 29%, 23%, and 20% for cohort 1 – first line, cohort 1 – second/third line, and cohort 2, respectively. In total, 105 patients received any boost doses, and 14 had repeated boost phases. Best overall response to nivolumab ± nivolumab + ipilimumab was 48% (95% CI 32-64), 27% (95% CI 15-43), and 33% (95% CI 23-44), respectively. The median OS for cohort 1 – first line was 16.4 months (95% CI 7.3 – 28.5), for cohort 1 – second/third line was 8.3 months (95% CI 5.3 – 19.3), and cohort 2 second/third line was 7.6 months (95% CI 5.0 – 14.9):
The median PFS for cohort 1 – first line was 3.0 months (95% CI 1.8 – 6.8), for cohort 1 – second/third line was 1.9 months (95% CI 1.7 – 5.8), and cohort 2 second/third line was 1.9 months (95% CI 1.8 – 3.2):
Dr. Grimm concluded her presentation discussing the final results of TITAN-TCC in metastatic urothelial carcinoma with the following concluding statements:
- Despite meaningful clinical activity of the TITAN-TCC approach in cohort 1 – first line, starting treatment with nivolumab monotherapy appears inadequate given the aggressiveness of metastatic urothelial carcinoma
- In second/third line, nivolumab + ipilimumab boosts with escalating dose of ipilimumab (cohort 1 – second/third line) did not improve ORR vs nivolumab monotherapy as reported in the literature
- Second and third line patients (cohort 2) may benefit from a tailored approach with high dose ipilimumab regarding response and survival outcomes
Presented by: Marc-Oliver Grimm, MD, Jena University Hospital, Jena, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
Reference:
- Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.