Research Frontier The second-line immune combination regimen for the treatment of advanced kidney cancer is worth paying attention to——nivolumab + ipilimumab

Immuno-oncology (IO) therapies, which include immune checkpoint inhibitor (ICI) monotherapy and combination therapy, have become the standard of care
for first- and second-line treatment for patients with advanced renal cell carcinoma (aRCC).
Despite the good efficacy of IO, some patients still develop resistance/toxicity to ICI and disease progression in the first-line treatment of aRCC, and the best treatment regimen for the second line and subsequent treatment of such patients is inconclusive and worth exploring
.

FRACTION-RCC is a randomized, adaptive platform-based phase II clinical trial designed to evaluate the efficacy and safety outcomes
of multiple IO combination regimens in patients with aRCC who have progressed after prior IO therapy.
This article focused on the analysis of clinical outcomes and follow-up data
in patients randomized to nivolumab + ipilimumab.

Patients were included with histologically confirmed advanced clear cell carcinoma of the kidney, a life expectancy of ≥ 3 months, Karnofsky functional status score of ≥70%, and disease progression during/after any prior IO (anti-PD-1/anti-PD-L1 or anti-CTLA-4) treatment, excluding patients
previously treated with anti-CTLA-4 plus anti-PD-1/PD-L1 。 Enrolled patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg combination therapy (q3 w, 4 doses), followed by nivolumab monotherapy (480 mg, q4 w) for 2 years or until disease progression, toxicity, or discontinuation as specified in the protocol
.
The primary outcomes were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) at 24 weeks of treatment, safety and tolerability up to two years, and overall survival (0S) as additional exploration endpoints
.

The median follow-up of the 46 included patients was 33.
8 (range: 24.
1-45.
2) months, the ORR was 17.
4% (95% CI 7.
8 to 31.
4), 8 patients (17.
4%) achieved partial remission, 19 patients (41.
3%) had stable disease, and 14 patients (30.
4%) had disease progression
.
Patients had a median response time of 2.
9 (range: 1.
5 to 12.
7) months and a median DOR of 16.
4 (range: 2.
1+ to 27.
0+) months
.
Of the 8 patients with partial response, 5 patients had a 50% response rate ≥, and 4 patients had a 75% reduction in tumor burden>
75%.

Table 1 Objective response rate of patients

At 24 weeks of treatment, the patient's PFS was 43.
2% and the median OS was 23.
8 months (95% CI 13.
2 - not achieved).

Among the safety outcomes, 13 patients (28.
3%) experienced grade 3/4 treatment-related adverse events (TRAEs), 7 patients (15.
2%) experienced grade 3/4 immune-mediated adverse events, and no patients died
due to TRAEs.

Patients with aRCC who have progressed prior to IO therapy are expected to achieve sustained clinical benefit with nivolumab + ipilimumab, and the safety profile of this combination regimen is manageable and consistent
with previously reported safety.

References:

Choueiri TK, Kluger H, George S, Tykodi SS, Kuzel TM, Perets R, Nair S, Procopio G, Carducci MA, Castonguay V, Folefac E, Lee CH, Hotte SJ, Miller WH Jr, Saggi SS, Lee CW, Desilva H, Bhagavatheeswaran P, Motzer RJ, Escudier B.
FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy.
J Immunother Cancer.
2022 Nov; 10(11):e005780.
doi: 10.
1136/jitc-2022-005780.
PMID: 36328377; PMCID: PMC9639138.