Efficacy of a tailored approach with nivolumab and nivolumab/ipilimumab as immunotherapeutic boost in metastatic renal cell carcinoma: Final results of TITAN-RCC

The combination of nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo+ipi) is an approved 1st line (1L) therapy for patients with metastatic renal cell carcinoma (mRCC) and intermediate / poor risk. TITAN-RCC investigated a response-based approach with nivo induction and nivo+ipi boost in non-responders. We report final study results for 1L and 2L (after TKI) patients. From OCT 2016 to DEC 2018 207 patients with intermediate/poor risk mRCC started nivo induction (Q2W, 240 mg). Patients with early progressive disease (PD, week 8) or non-responders at week 16 (stable disease [SD]/PD) received 2-4 doses nivo+ipi. Responders to nivo induction (complete/partial response [CR/PR]) continued with nivo maintenance but could receive nivo+ipi for later PD. The primary endpoint was confirmed objective response rate (ORR) per RECIST in 1L and 2L. Secondary endpoints included efficacy of nivo induction, response to boost, progression free (PFS) and overall survival (OS), and safety. Of the 207 patients, 109 were 1L and 98 2L. Median age was 65 yr, 71 % of patients had intermediate and 25 % poor risk. Confirmed response to nivo induction was 28 % in 1L and 18 % in 2L. After 33.6 months from last patient first treatment and 15.9 months median follow-up, ORR for nivo ± nivo+ipi was 36 % in 1L (significant >25 %, p<0.05) and 32 % in 2L. Irrespective of time point, 44% (1L) and 53% (2L) of patients receiving boosts for PD upon nivo improved in best response. PFS was 6.3 months (95 % CI 3.7-10.1) in 1L and 3.7 months (95 % CI 1.8-4.5) in 2L. OS was 32.0 months (95 % CI 22.9-39.4) in 1L and 25.9 months (95 % CI 17.8-33.7) in 2L. No new safety signals emerged.Table: 1450MOResponse to nivo+ipi boost1L1L1L2L2L2LInitial effectSD (n=21)PD (n=28)all (n=17)SD (n=17)PD (n=42)all (n=11)Start of first boost cycleweek 8/16week 8/16>week 16 (late boost)week 8/16week 8/16>week 16 (late boost)CR, n (%)1 (5)---3 (7)-PR, n (%)4 (19)3 (11)3 (18)-7 (17)2 (18)SD, n (%)13 (62)8 (29)6 (35)12 (71)12 (29)4 (36)PD, n (%)3 (14)17 (61)6 (35)4 (24)17 (40)4 (36)Not evaluable, n (%)--2 (12)1 (6)3 (7)1 (9) Open table in a new tab Nivo+ipi boosts improve outcomes compared to nivo monotherapy. Responses were also observed after progression during nivo maintenance suggesting a potential role as rescue strategy. However, overall efficacy of our tailored approach appears to be inferior compared to upfront nivo+ipi treatment.