Second-line nivolumab/ipilimumab boost improves ORR in metastatic urothelial carcinoma

In patients with metastatic urothelial carcinoma who completed platinum-based chemotherapy, treatment with nivolumab and a nivolumab/ipilimumab boost significantly improved ORR compared with nivolumab monotherapy. This was demonstrated in the phase 2 TITAN-TCC trial.

Nivolumab is an approved treatment after platinum-based chemotherapy in metastatic urothelial carcinoma [1]. The phase 2 TITAN-TCC trial (NCT03219775) was designed to evaluate a nivolumab/ipilimumab boost for patients who do not respond to 4 cycles of nivolumab. The primary endpoint was confirmed objective response rate (ORR) 30 weeks after the start of second-line nivolumab. Prof. Marc-Oliver Grimm (University Hospital Jena, Germany) presented the results [2].

The trial enrolled 83 patients, of whom 33 (16%) patients had stable disease and 31 (37%) patients had progressive disease after 4 doses of nivolumab. These patients received 2–4 doses of a nivolumab/ipilimumab boost. Participants who had a complete or partial response after 4 doses of nivolumab (n=39) continued with nivolumab maintenance therapy; 6 of these patients received a nivolumab/ipilimumab boost during maintenance therapy.

The median follow-up time was 5.6 months. ORR with nivolumab monotherapy was 20% (17/83); ORR with nivolumab with or without boost was 33% (27/83). By way of comparison: in CheckMate 275, ORR was 19.6% [1]. Patients with PD-L1 expression in ≥1% of tumour cells (n=28) had a higher ORR compared with PD-L1-negative patients (46% vs 24%; see Figure). Of patients with initial stable disease after nivolumab monotherapy (n=13), 4 patients achieved a partial or complete response upon boost. Of patients with progressive disease after nivolumab monotherapy (n=31), 6 achieved a partial or complete response upon boost. No new safety signals emerged.

Figure: Efficacy in intention-to-treat population, stratified by PD-L1 expression [2]



BOR, best objective response; CR, complete response; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease

“In patients with metastatic urothelial carcinoma, second-line treatment with nivolumab and nivolumab/ipilimumab boosts in non-responders significantly improves ORR compared with nivolumab monotherapy,” concluded Prof. Dr Grimm.

1. Sharma P, et al. Lancet Oncol. 2017;18:312–322.
2. Grimm M-O, et al. Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC). Abstract 411, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024