No Survival Difference for Front-Line Combination Regimens in Intermediate- and Poor-Risk Clear Cell RCC: Real-World Outcomes
A large retrospective study of real-world patients with renal cell carcinoma (RCC) showed similar survival outcomes for patients with intermediate- or poor-risk disease regardless of whether they were treated with the combination of axitinib plus pembrolizumab or ipilimumab plus nivolumab. These findings were presented by Zarrabi et al during the 2021 ASCO Annual Meeting (Abstract 4551).
“Clinicians can take some reassurance that both combinations provide a survival benefit, and there seems to be no harm in choosing one combination over the other based on this analysis,” said Kevin Zarrabi, MD, a second-year hematology/oncology fellow at Fox Chase Cancer Center and lead author of the study.
Front-Line Treatment for RCC
Front-line treatment for patients with metastatic clear cell RCC has changed rapidly in the last few years, first with the approval of targeted agents like sunitinib and everolimus, and later with the approval of combination axitinib plus pembrolizumab and ipilimumab plus nivolumab, Dr. Zarrabi said.
“Both of the newer combination regimens showed marked advances in progression-free survival in patients with kidney cancer and were considered giant leaps forward,” he explained. “With no prospective data comparing the regimens, questions remained about which is the better option for these patients.”
Axitinib/Pembrolizumab vs Ipilimumab/Nivolumab
To evaluate that question, Dr. Zarrabi and colleagues used data from 821 patients with metastatic clear cell RCC treated with either axitinib plus pembrolizumab (n = 259) or ipilimumab plus nivolumab (n = 562) taken from the nationwide Flatiron Health electronic health records–derived, de-identified database. All patients in the study had International Metastatic RCC Database Consortium (IMDC) intermediate- or poor-risk disease.
- The median overall survival was not reached for axitinib plus pembrolizumab and was 22 months for ipilimumab plus nivolumab.
- The 12-month survival was 68.5% for patients treated with axitinib/pembrolizumab and 65.8% for patients treated with ipilimumab/nivolumab.
“By looking at real-world patients, we are looking at the actual outcomes in patients across the country treated at academic or community practices,” Dr. Zarrabi said. “This provides an advantage because clinical trials often have strict inclusion or exclusion criteria and do not account for many patients that we encounter in the general population.”
At 12 months’ follow-up, there was no significant difference in survival between patients treated with either combination regimen. The median overall survival was not reached for axitinib plus pembrolizumab and was 22 months for ipilimumab plus nivolumab. The 12-month survival was 68.5% for patients treated with axitinib/pembrolizumab and 65.8% for patients treated with ipilimumab/nivolumab.
“This large, real-world retrospective analysis—with the caveat of limited follow-up—shows that both therapies are appropriate for [International Metastatic RCC Database Consortium] intermediate- and poor-risk disease, and appear to confer similar survival,” said Daniel M. Geynisman, MD, Associate Professor in the Department of Hematology/Oncology at Fox Chase and senior author of the study. “Therefore, clinicians should take into account multiple clinical factors when making treatment decisions for these patients.”
Clinicians may choose one regimen over another due to patient comorbidities, familiarity with study data, or comfort with administering the drugs, Dr. Zarrabi said.
Dr. Geynisman noted that one key remaining question will be how these outcomes evolve over time and whether they remain similar for both regimens, and the team will be looking at that with longer term follow-up data.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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