Real-World Study Shows Fast Uptake of Immunotherapy-Based Combinations in Frontline RCC

The FDA approvals of immunotherapy-based combinations as frontline therapy led to a substantial increase in their use in patients with metastatic renal cell carcinoma (mRCC) in the community setting, leading to a greater use of TKI monotherapy as second- and third-line therapies, according to findings from a study that were presented at the 2022 Genitourinary Cancers Symposium.

The results highlighted a trend toward the increased use of dual checkpoint inhibition and checkpoint/VEGF inhibition after their FDA approvals in April 2018 (third/fourth quarter 2018, 46.6%; first and second quarter 2019, 50.2%) and April 2019 (first and second quarter 2019, 7.7%; third and fourth quarter 2019, 32.2%), respectively.

Notably, the use of single-agent TKIs decreased from 53.4% in the third and fourth quarter of 2018 to 42.1% in the first and second quarter of 2019 to 24.0% in the third and fourth quarter of 2019.

“This large real-world study examined use of new FDA-approved mRCC treatments and their impact on [the] treatment paradigm. The results show a rapid adaptation of these newer treatments in the community oncology settings,” the study authors wrote.

Several checkpoint inhibitor and TKI combinations have been approved by the FDA for the frontline treatment of patients with mRCC over past few years. However, data are few and far between regarding the real-world use and sequence of available regimens in mRCC, particularly in the community setting.

To better understand current community practice patterns, investigators compiled data from The US Oncology Network, pooling more than 1300 providers from over 480 sites in the United States from January 1, 2018, to December 31, 2020.

Eligible patients included those with mRCC who had received either the combination of ipilimumab (Yervoy) plus nivolumab (Opdivo), pembrolizumab (Keytruda) plus axitinib (Inlyta), or avelumab (Bavencio) plus axitinib, or single-agent axitinib, cabozantinib (Cabometyx), pazopanib (Votrient), or sunitinib (Sutent) as frontline therapy until September 30, 2020.

A total of 1538 patients were eligible for inclusion in the study. Most patients had received dual checkpoint inhibition (41.6%; n = 641) followed by TKI monotherapy (40.2%; n = 618) and a checkpoint/VEGF inhibitor combination (18.1%; n = 279). However, by the third quarter of 2020, most patients were receiving dual checkpoint inhibition (41.9%) or checkpoint/VEGF inhibition (31.3%) followed by TKI monotherapy (26.9%).

The median patient age was 67.4 years (interquartile range, 57.8-76.0). Most patients were male (69.7%; n = 1,076) and White (69.5%; n = 1,081); 79.8% (n = 1208) had clear cell histology.

Most patients (86.6%; n = 1338) had intermediate- and poor-risk disease according to the International Metastatic RCC Database Consortium risk model.

Over the course of the study period, 34.7% of patients (n = 535) received second-line therapy: 19.0% (n = 53) in the checkpoint/VEGF group; 38.5% (n = 247) in the dual checkpoint inhibition group; and 38.0% (n = 235) in the TKI monotherapy group. A total of 34.7% of patients (n = 186) received third-line therapy; less than 42.0% (n = 12), 33.6% (n = 83), and 38.7% (n = 91) across the groups, respectively.

The most common second-line therapies in patients who received prior dual checkpoint inhibition were cabozantinib (48.6%; n = 120) and pazopanib (12.1%; n = 30); the most common third-line treatments were cabozantinib (20.5%; n = 17), everolimus (Afinitor) plus lenvatinib (Lenvima; 18.1%; n = 15), and axitinib (10.8%; n = 9).

In patients who received prior checkpoint/VEGF inhibition, the most common second-line treatments were cabozantinib (50.9%; n = 27) and ipilimumab plus nivolumab (22.6%; n = 12); less than 5 patients (<42.0%) received cabozantinib as third-line therapy.

Patients who received a single-agent TKI in the frontline setting received nivolumab (44.7%; n = 105) and ipilimumab plus nivolumab (19.6%; n = 46) most commonly in the second-line setting; the most common third-line treatments were cabozantinib (22.0%; n = 20) and axitinib (16.5%; n = 15).

“Longer follow-up is needed to assess their clinical impact and optimal treatment strategy in subsequent setting[s],” concluded the study authors.

Reference

1. Shah NJ, Sura S, Shinde R, et al. Real-world assessment of changing treatment patterns and sequence for patients with metastatic renal cell carcinoma (mRCC) in the first-line (1L) setting. J Clin Oncol. 2022;40(suppl 6):302. doi:10.1200/JCO.2022.40.6_suppl.302