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Immuno-oncology (IO) combinations have emerged as the standard of care for frontline metastatic clear cell renal cell carcinoma (mccRCC) treatment, and their use has steadily increased since 2018, according to research presented at the .

Joseph Vento, MD, of Vanderbilt University Medical Center in Nashville, and colleagues analyzed data to identify trends in 515 mccRCC patients in ASCO's Discovery real-world database treated with IO combinations from 2018 to 2021.

One notable trend was the use of IO-tyrosine kinase inhibitor (TKI) combinations, which increased from 31% of patients in 2018 to 44% in 2021.

Vento, a postdoctoral research fellow in the Department of Biomedical Informatics, discussed this and other trends, as well as their implications, in the following interview.

Why did you decide to undertake this study?

Vento: Systemic treatments in advanced renal cell carcinoma changed dramatically in recent years as multiple IO-based combination therapies demonstrated improved survival outcomes in large randomized clinical trials relative to prior standards of care.

As there are no validated biomarkers to guide selection of one of these regimens over another for a specific patient, we were interested in comparing utilization trends of these different IO-based regimens in the United States since the times of their approval. Further, we wanted to report on outcomes in patients treated with these IO combinations in real-world populations, which can differ significantly from the populations who enroll in clinical trials.

What is the ASCO CancerLinQ Discovery Database?

Vento: The ASCO CancerLinQ Discovery Database synthesizes and fully de-identifies electronic health record data from millions of cancer patients who are seen at partnering cancer centers across the U.S.

CancerLinQ focuses on partnering with centers from a variety of practice sizes and geographic locations to synthesize patient data from cohorts representative of the diverse U.S. cancer population. This project studied the kidney cancer subset of this database, and the patient data were further filtered to identify only metastatic clear cell RCC patients who received front-line IO-based therapy.

What was the most commonly used drug combination, and why do you think that was?

Vento: This study focused on comparing the IO-IO combination nivolumab-ipilimumab, approved in 2018, with IO-TKI combinations, the first of which -- pembrolizumab-axitinib -- was approved in 2019. We report that from 2019 to 2021, of all patients receiving any front-line IO-based therapy, the percentage of patients receiving IO-TKI therapy increased each year and by 2021 passed nivolumab-ipilimumab as the most frequently used front-line IO therapy.

This may indicate that providers and patients are showing some preference to IO-TKI therapy over IO-IO therapy. Further studies are needed to examine why this is the case, but an increased risk of serious and irreversible immune-related adverse events with IO-IO combination therapy and a preference for oral therapies -- the TKI in these regimens is always taken orally, whereas the IO therapies are intravenous -- may play roles in this trend.

Another trend you analyzed was time to treatment discontinuation with the various IO combinations. Why did you examine this and what did you find?

Vento: Oncology trials in the metastatic setting frequently use progression-free survival (PFS) as a surrogate for overall survival (OS). In this database, there was not sufficiently granular radiologic or clinical data for patients on IO combination therapy to report PFS.

However, the database contains excellent medication data, including start and stop dates, and thus we focused on time to treatment discontinuation (TTD) as a surrogate marker instead of PFS. While not a perfect replacement, it allows us to perform more robust survival analyses on our dataset population, and thus give rough approximations of how these outcomes compare with those reported in large clinical trials.

We found the median TTD was significantly shorter for both IO-IO and IO-TKI in the CancerLinQ Discovery Dataset than the median PFS reported in respective large randomized clinical trials, which could indicate that real-world performance of these therapies is worse than in clinical trial populations.

You also examined trends in overall survival. What did you find here, and are there any implications?

Vento: Overall survival is an outcome that is very meaningful to patients in understanding their anticipated disease course. We found that the kidney cancer subset of the CancerLinQ Discovery database does not yet have sufficient longitudinal data to report on median OS in these patients receiving IO-based combination therapies, which is actually quite encouraging as these are patients with metastatic kidney cancer who are living for many years!

We are hopeful that with additional years of gathering data, we can report the median OS for these cohorts as well to compare with respective clinical trials.

From this work reported at the ASCO Quality Care Symposium, we can comment that the OS survival curves between the IO-IO and IO-TKI regimens appear quite similar, and draw the general conclusion that IO-combination therapies remain very effective treatment options in real-world metastatic RCC patients.

Read the study here.