Dr Grünwald on Tumor Burden Outcomes From the CLEAR Trial in Advanced RCC

Viktor Grünwald, MD, PhD, professor of interdisciplinary genitourinary oncology at the University Hospital Essen, discusses findings from the phase 3 CLEAR trial (NCT02811861), highlighting the differences in tumor burden between patients with advanced renal cell carcinoma (RCC) treated with lenvatinib (Lenvima) plus pembrolizumab (Keytruda) vs those treated with sunitinib (Sutent).

The analysis sought to observe changes in tumor burden between treatment arms. Results presented at the 2024 ASCO Annual Meeting indicated that at the time of overall disease progression, the tumor burden of target lesions was lower in patients treated with lenvatinib plus pembrolizumab vs those treated with sunitinib, Grünwald states. Patients treated with lenvatinib plus pembrolizumab exhibited a –48.1% median change in sums of targeted lesions from baseline vs –17.4% in patients treated with sunitinib.

As part of the analysis, during survival follow-up, investigators also evaluated subsequent anticancer therapy. The results showed that more patients in the sunitinib arm (n = 246) received subsequent anticancer therapy compared with those in the lenvatinib plus pembrolizumab arm (n = 181), Grünwald notes. Seventy patients in the combination arm received cabozantinib (Cabometyx) as their first subsequent therapy and experienced a median time to discontinuation of 13.2 months compared with 7.1 months among the 25 patients who received cabozantinib as first subsequent therapy in the sunitinib arm. Axitinib (Inlyta) was administered to 20 patients as first subsequent therapy in the combination arm; these patients had a median discontinuation time of 23.7 months vs 12.6 months among the 14 patients who received axitinib as first subsequent therapy in the sunitinib arm.

These findings suggest that the lower tumor burden observed at progression with lenvatinib plus pembrolizumab could enhance the effectiveness of subsequent therapies, such as cabozantinib and axitinib, Grünwald explains. Although these findings are observational, they highlight the importance of exploring how initial tumor burden reduction with frontline therapy could affect the efficacy of subsequent treatments, which could help inform future therapeutic strategies in advanced RCC, Grünwald concludes.