Updated results affirm immunotherapy combo as new standard for advanced kidney cancer
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Key takeaways:
- The lenvatinib-pembrolizumab group had longer median PFS and median OS than the sunitinib group.
- The combination should remain the new standard front-line therapy for clear-cell advanced renal cell carcinoma, according to researchers.
A combination of lenvatinib and pembrolizumab continued to provide a greater survival benefit than sunitinib among patients with advanced renal cell carcinoma, an updated analysis of the randomized phase 3 CLEAR study showed.
Extended follow-up of the randomized trial, published in The Lancet Oncology, revealed significantly longer PFS and OS among patients who received the immunotherapy combination as front-line treatment for metastatic disease.
“The durable clinical response and the survival benefit continue to affirm [use of] pembrolizumab and lenvatinib as a first-line combination in patients with advanced renal cell carcinoma,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, told Healio.
Background, methodology
The CLEAR trial examined the safety and efficacy of the PD-1 inhibitor pembrolizumab (Keytruda, Merck) in combination with lenvatinib (Lenvima, Eisai) — a kinase inhibitor — in patients with clear-cell advanced renal cell carcinoma who had not received previous systemic anticancer therapy.
The trial included 1,069 adults (median age, 62 years; 74% men) randomly assigned in a 1:1:1 ratio to receive either oral lenvatinib dosed at 20 mg per day in 21-day cycles plus IV pembrolizumab dosed at 200 mg every 21 days (n = 355), oral lenvatinib dosed at 18 mg per day plus oral everolimus dosed at 5 mg per day in 21-day cycles (n = 357), or oral sunitinib (Sutent, Pfizer) dosed at 50 mg per day (4 weeks on and 2 weeks off; n = 357).
PFS assessed by RECIST version 1.1 served as the study’s primary endpoint.
The protocol-prespecified updated analysis included updated OS and PFS data for the intent-to-treat population. It did not include data from the lenvatinib-everolimus group.
Median follow up for PFS was 27.8 months (interquartile range [IQR], 20.3-33.8) in the lenvatinib-pembrolizumab group and 19.4 months (IQR, 5.5-32.5) in the sunitinib group. Median follow-up for OS was 33.7 months (IQR, 27·4-36·9) in the lenvatinib-pembrolizumab group and 33.4 months (IQR, 26.7-36.8) in the sunitinib group.
Data cutoff for the analysis occurred March 31, 2021.
Results
The updated analysis showed significantly longer median PFS of 23.3 months (95% CI, 20.8-27.7) in the lenvatinib-pembrolizumab group compared with 9.2 months (95% CI, 6-11) in the sunitinib group (stratified HR = 0.42; 95% CI, 0.34-0.52).
Researchers also observed significantly longer median OS with the combination (median not yet reached; 95% CI, 41.5 to not estimable) compared with sunitinib (median not yet reached; 95% CI, 38.4 to not estimable; HR = 0.72; 95% CI, 0.55-0.93).
Clinical implications
The follow-up results provide a measure of reassurance that the combination of lenvatinib plus pembrolizumab should remain the new standard front-line therapy for patients with clear-cell advanced renal cell carcinoma, according to Choueiri.
The findings also provide evidence that the initial high response rates are “no fluke,” he said, especially given that median PFS with the combination immunotherapy is approximately 2 years at this latest assessment.
“Here we offered 8 more months of follow-up, and the results remained consistent across risk groups,” Choueiri told Healio. “What's also important is there were no new safety signals.”
For more information:
Toni K. Choueiri, MD, can be reached at toni_choueiri@dfci.harvard.edu.
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