In an analysis reported in JAMA Network Open, Sharp et al identified the frequency of use of postprotocol PD-1/PD-L1 inhibitors in control group patients receiving the tyrosine kinase inhibitor sunitinib in randomized trials comparing PD-1/PD-L1 inhibitor–containing combination therapy vs sunitinib for the first-line treatment of advanced renal cell carcinoma.

As stated by the investigators, “Immunotherapy is associated with improved survival rates in advanced kidney cell carcinoma after progression on first-line [tyrosine kinase inhibitor] treatment. It is unknown whether and to what degree patients in the control arm receive [postprotocol] immunotherapy in trials comparing combination immunotherapy regimens with [tyrosine kinase inhibitor] in first-line advanced renal cell carcinoma.”

Study Details

The analysis included data from six trials and updates from three of the trials (reported in English between January 2015 and February 2021) that compared first-line combination therapy with a PD-1/PD-L1 inhibitor plus another immunotherapy agent or a tyrosine kinase inhibitor vs sunitinib. The objective of the analysis was to determine the proportion of patients in the sunitinib control groups who received PD-1/PD-L1 inhibitor therapy as second-line treatment after discontinuing sunitinib.

Key Findings

A total of 2,565 patients were assigned to sunitinib groups in the trials, with numbers of patients ranging from 328 to 546. Of these, 2,069 (80.7%) had discontinued sunitinib at last data cutoff, with proportions discontinuing treatment ranging from 70.1% to 97.3%.

Among the 2,069 patients who discontinued sunitinib, 1,403 (54.7%) received any postprotocol therapy, with proportions across studies ranging from 32.9% to 57.7%. A total of 932 (45.0%) of the 2,069 patients who discontinued sunitinib received postprotocol PD-1/PD-L1 inhibitor treatment as second-line therapy, with proportions across studies ranging from 28.4% to 53.1%. The 932 patients who received postprotocol PD-1/PD-L1 inhibitor therapy accounted for 66.4% of patients receiving any postprotocol therapy, with proportions across studies ranging from 60.5% to 74.8%.

The investigators stated, “In this systematic review, use of postprotocol immunotherapy among patients in the control arm was low, which may be associated with an overestimation of the clinical benefit of the combination immunotherapy regimen.”

They concluded, “We found that the proportion of patients in the control arm receiving [postprotocol] immunotherapy is low in randomized clinical trials of first-line combination immunotherapy regimens for advanced renal cell carcinoma. Appropriate use of [postprotocol] therapy is essential to answering the question of whether a combination or sequential treatment strategy with immunotherapy is superior.”

Vinay Prasad, MD, MPH, of the Department of Medicine, University of California, San Francisco, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.