IMMUNOTHERAPY combined with a targeted kinase inhibitor induces longer overall survival than the current standard treatment in patients with advanced kidney cancer. The results of the Phase III CLEAR study were presented at the American Society of Clinical Oncology (ASCO) 2021 by Dr Toni Choueiri, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, and suggest that the combination therapy be considered as a first-line treatment for patients with advanced renal cell carcinoma.
The study involved three different medication administrations to three patient groups: the combination of lenvatinib, an oral kinase inhibitor targeting the proteins required to form the blood vessels supplying a tumour, and pembrolizumab, a checkpoint inhibitor that aids the immune system to attack cancer; sunitinib, a multikinase inhibitor, which is the current standard treatment, its use in the treatment of advanced kidney cancer carrying a poor prognosis; and the combination of lenvatin and everolimus, a drug that targets mTOR, and a combination that is approved for patients with lupus whose disease progresses following sunitinib treatment.
Sunitinib was the comparison drug in this study. Progression-free survival (PFS) was the primary endpoint, which refers to the length of time during and after treatment before a disease gets worse.
Individuals who received lenvatinib/pembrolizumab reported the longest PFS, longest overall survival, and highest response rates. Both combination therapies were superior to sunitinib alone, with lenvatinib/pembrolizumab attaining median PFS of 23.9 months and lenvatinib/everolimus a PFS of 14.7 months, versus 9.2 months for sunitinib. Lenvatinib/pembrolizumab achieved a 24-month overall survival rate of 79.2%, lenvatinib/everolimus 66.1%, and sunitinib 70.4%. The response rates refer to the confirmed objective response rate (percentage of patients whose disease shrank) and the complete response rate (total tumour shrinkage), which in the patients receiving lenvatinib/pembrolizumab were 71% and 16.1%, lenvatinib/everolimus were 53.5% and 9.8%, and sunitinib were 35.1% and 4.2%, respectively.
“The rate of responses and complete responses, and the progression-free survival were the longest we have seen to date in a Phase III combination of a targeted VEGF inhibitor and an immune checkpoint inhibitor,” said Dr Choueiri. This study represented the last of the clinical trials that were instigated to compare immunotherapy and targeted drug combinations to the current standard sunitinib.
The results present new options for advanced kidney cancer standard-of-care and the potential of a better prognosis with treatment with immune checkpoint inhibitors, either as a checkpoint inhibitor plus a kinase inhibitor or as a combination of two checkpoint inhibitors.