Trial eligibility linked to better outcomes after immunotherapy for renal cell carcinoma
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NASHVILLE, Tenn. — Patients with renal cell carcinoma who met eligibility criteria for pivotal phase 3 trials achieved significantly longer survival after combination immunotherapy than trial-ineligible patients, according to study results.
The findings — presented at International Kidney Cancer Symposium: North America — suggest additional treatment options and new strategies to allow these patients to participate in prospective trials are needed, researchers concluded.
Clinical trials designed to evaluate immunotherapy-based regiments for renal cell carcinoma often have extensive inclusion and exclusion criteria. However, it is not clear if these criteria have meaningful impact on outcomes, researcher Nathan Reynolds, DO, MPH, third-year resident at Cleveland Clinic, told Healio.
“Enrollment into clinical trials is challenging for people with cancer for a number of reasons,” Reynolds said. “We wanted to look at the outcomes of real-world patients who were treated with these regimens based on whether they were or were not eligible for the trials that led to their initial approvals.”
Reynolds and colleagues identified patients treated at Cleveland Clinic who received front-line therapy with one of two immunotherapy combinations — ipilimumab (Yervoy, Bristol Myers Squibb) and nivolumab (Opdivo, Bristol Myers Squibb), or axitinib (Inlyta, Pfizer) and pembrolizumab (Keytruda, Merck).
Researchers characterized patients as clinical trial eligible or ineligible based on the key inclusion and exclusion criteria used for phase 3 trials of each combination — CheckMate 214 for ipilimumab-nivolumab and KEYNOTE-426 for axitinib-pembrolizumab.
International Metastatic RCC Database Consortium criteria appeared similar between trial-eligible and trial-ineligible patients in both cohorts.
Investigators used Fisher’s exact test and log rank test to compare objective response rate, PFS and OS between trial-eligible and trial-ineligible patients.
The analysis included 62 patients treated with axitinib-pembrolizumab (trial eligible, n = 37; trial ineligible, n = 25). The most common reasons for trial ineligibility included lab abnormalities (n = 11), histology (n = 10) and brain metastases (n = 3).
Results showed significantly improved OS (median, 27.37 months vs. N/A; 2-year OS, 74% vs. 59%; 5-year OS, 51% vs. NA; P = .04) among trial-eligible patients.
The analysis included 103 patients treated with ipilimumab-nivolumab (trial eligible, n = 44; trial ineligible, n = 59). The most common reasons for trial ineligibility included brain metastases (n = 16), lab abnormalities (n = 16) and histology (n = 14).
Results showed significantly improved PFS (median, 21.98 months vs. 6.87 months; 2-year PFS, 48% vs. 24%; 5-year PFS, 40% vs. N/A; P = .0025) and OS (median, 71.49 months vs. 13.96 months; 2-year OS, 77% vs. 41%; 5-year OS, 57% vs. N/A; P < .0001) among trial-eligible patients.
Despite the survival advantages observed among trial-eligible patients in both analyses, researchers observed no statistically significant differences in radiographic response to either combination regimen based on trial eligibility.
“I think these findings introduce an interesting question of how we incorporate real-world patients who may not be eligible based on strict inclusion or exclusion criteria,” Reynolds said. “If they have incidental brain metastases that we wouldn’t have picked up, if they have [chronic kidney disease] or maybe their renal function isn’t great at baseline, is there some flexibility there?”
More analyses must be conducted to dive deeper into the data, Reynolds said.
“A lot of trials by design have great intentions with inclusion and exclusion criteria, and a lot of thought goes into why they have what they have,” Reynolds said. “But sometimes in the clinic there are patients who would’ve been ineligible for the trials that got many of our medications approved. We’re hoping, moving forward, that a framework can be developed to look at how we can include these real-world patients who otherwise would not have been eligible.”
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Reynolds N, et al. Abstract 53. Presented at: IKCS: North America; Nov. 9-11, 2023; Nashville, Tenn.
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