(UroToday.com) On Sunday, September 11,2022, in the Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Grimm presented the final results of the TITAN-RCC trial, assessing a tailored approach to systemic therapy in patients with metastatic renal cell carcinoma (mRCC). A combination immune checkpoint inhibitor approach with nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo+ipi) is an approved first-line treatment approach in mRCC and intermediate / poor risk disease. However, there is significant toxicity so a tailored approach has been assessed in a number of trials.
TITAN-RCC included patients receiving both first-line treatment and second-line treatment following initial tyrosine kinase inhibitors. The study used a response-based approach with nivo induction and nivo+ipi boost in non-responders.
Between October 2016 and December 2018, 207 patients with intermediate/poor risk mRCC started initial nivo induction (Q2W, 240 mg). Patients with early progressive disease (PD, week 8) or non-responders at week 16 (stable disease [SD]/PD) received 2 to 4 doses of nivo+ipi. In contrast, those who were initial responders to nivo induction (complete/partial response [CR/PR]) continued with nivo maintenance but could receive nivo+ipi for later progressive disease. The primary endpoint was confirmed objective response rate (ORR) per RECIST in both the first- and second-line setting. Secondary endpoints included efficacy of nivo induction, response to boost, progression free (PFS) and overall survival (OS), and safety.
Among 207 enrolled patients, 109 were treated in the first-line setting and 98 were treated following initial TKI therapy. Among included patients, the median age was 65 years of age. Among the 207 patients, 71 % had intermediate and 25 % had poor risk disease.
A confirmed response to nivo induction was seen in 28% of patients in the first-line and 18% in the second-line setting. After 33.6 months from last patient’s first treatment and at 15.9 months median follow-up, the objective response rate for nivo ± nivo+ipi was 36% in the first-line setting (significant >25 %, p<0.05) and 32% in the second-line setting.
Whether due to initial early progressive disease or non-response or a delayed progressive disease, 44% of patients who started first-line therapy with nivo monotherapy and 53% of patients in the second-line setting received ipi boosts for PD improved in best response.
Progression-free survival was 6.3 months (95 % CI 3.7-10.1) in first-line and 3.7 months (95 % CI 1.8-4.5) in second-line. Correspondingly, overall survival was 32.0 months (95 % CI 22.9-39.4) in first-line and 25.9 months (95 % CI 17.8-33.7) in second-line.
With this final analysis, the authors identified no new safety signals.
Dr. Grimm concluded the nivo+ipi boosts following initial nivo monotherapy improve outcomes. While there was demonstrated potential with ipilimumab as a rescue strategy, these outcomes are inferior to initial upfront combination therapy. Thus, this tailored approach is not recommended.
Presented by: Marc-Oliver Grimm, MD, Professor and Chairman at Universitätsklinikum Jena, Jena, Germany
Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.