Use of First-Line Post-Protocol Immunotherapy Appears Low in Kidney Cell Carcinoma Clinical Trials

In a systemic review assessing the use of first-line post-protocol immunotherapy for patients with kidney cell carcinoma, investigators reported that use was low in randomized clinical trials among patients in the control group.

The number of patients with kidney cell carcinoma (KCC) receiving post-protocol first-line immunotherapy as part of a combination regimen in the control arm oc randomized clinical trials was low, according to the results of a systemic review published in JAMA Network Open

Data indicated that of the patients included in the study (n = 2565), 81% of those in the control arm were no longer on a Tyrosine kinase inhibitor (TKI) as of the last data cutoff. Additionally, 45% of patients who discontinued treatment with a TKI received post-protocol immunotherapy. Investigators also reported that 66.4% of patients in the control arm who underwent treatment with any kind of post-protocol therapy received immunotherapy.

“To our knowledge, this is the first investigation of control arm post-protocol immunotherapy administration after first-line treatment in advanced KCC. This is a notable area of inquiry because there are limited proven effective therapies for this disease, and appropriate use of lines of therapy is essential to provide the best outcomes for patients,” the study investigators wrote.

Investigators identified 6 clinical trials and 3 updated analyses that compared immunotherapy combinations with sunitinib (Sutent) in first-line advanced KCC that were published between 2015 and 2021. All trials had identical control arms wherein sunitinib was administered once a day at a dose of 50 mg with identical dose reduction strategies.

A total of 19.3% of patients continued to receive sunitinib at data cutoff across all trials. Of the patients who discontinued treatment with sunitinib, 54.7% received some manner of post-protocol therapy. Additionally, 36.3% of patients received post-protocol therapy and 18.4% received another form of post-protocol therapy.

Investigators reported that 4872 patients enrolled globally, 56.6% of whom enrolled in the United States, Canada, or Western Europe, and 43.4% were enrolled from other countries such as Argentina, Australia, Brazil, Chile, Colombia, Israel, Mexico, New Zealand, Russia, South Korea, Taiwan, and Ukraine.

“While providing combination immunotherapy regimens in the first-line setting has been reported to improve PFS [progression-free survival] in each of these trials, a relevant clinical question is whether the strategy of using multiple agents in a single treatment line, and thus depleting subsequent treatment options, is associated with improved OS [overall survival] compared with sequential therapy,” concluded investigators.


Sharp J, Khaki AR, Prasad V. Use of second-line immunotherapy in control arms of randomized clinical trials in kidney cancer: a systematic review. JAMA Netw Open. 2021;4(9):e2124728. doi:10.1001/jamanetworkopen.2021.24728