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Patients with advanced kidney cancer who received a targeted drug in combination with a checkpoint blocker immunotherapy drug had longer survival times than patients treated with the standard targeted drug, a researcher at the Dana-Farber Cancer Institute said, reporting results from one phase 3 clinical study.
The survival benefit shows that an immune checkpoint inhibitor along with a targeted kinase inhibitor drug "is important for the first-line treatment of patients with advanced renal cell carcinoma," said the authors of a study published today in the New England Journal of Medicine concurrently presented at the American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancers Symposium. The lead author is Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber.
The Phase 3 CLEAR trial results showed significant benefits from combining lenvatinib, an oral kinase inhibitor that targets proteins involved in the formation of blood vessels that supply a tumor, and pembrolizumab, one Checkpoint inhibitor, given by infusion, that helps the immune system attack the immune system cancer. Another group of patients received a combination of lenvatinib and everolimus, a drug that targets a protein, mTOR.
The comparator drug was sunitinib, a multiple kinase targeting inhibitor that was the standard of care for these patients with advanced kidney cancer who had a poor prognosis. However, the standard options now include treatment with immune checkpoint inhibitors, either as a combination of two checkpoint inhibitors or a checkpoint inhibitor plus a kinase inhibitor. These combinations have shown improved results compared to sunitinib in patients with advanced kidney cancer.
The results of the CLEAR study showed that those who received the combination of lenvatinib and pembrolizumab had not only longer overall survival, but also longer progression-free survival – the time before their disease got worse – and a higher response rate. In addition to lenvatinib plus pembrolizumab, the clinical trial also tested the combination of lenvatinib and everolimus, which is approved for patients with advanced kidney cancer whose disease progresses after treatment with sunitinib.
The primary endpoint of the study was progression-free survival (PFS). Both combinations were shown to be superior to sunitinib alone: lenvatinib / pembrolizumab achieved a mean PFS of 23.9 months compared to 9.2 for sunitinib; The PFS for lenvatinib / everolimus was 14.7 months.
The 24-month overall survival rate was 79.2% for lenvatinib / pembrolizumab, 66.1% for lenvatinib / everolimus, and 70.4% for sunitinib.
The confirmed objective response rate (percentage of patients whose disease shrank) was 71% for lenvatinib / pembrolizumab, 53.5% for lenvatinib / everolimus, and 35.1% for sunitinib. The rate of complete responses – total tumor shrinkage – was 16.1% in patients who received lenvatinib / pembrolizumab, 9.8% in the lenvatinib plus everolimus group, and 4.2% in the sunitinib group.
"The rate of response and full response, and progression-free survival, were the longest we've seen in a Phase 3 combination of a targeted VEGF inhibitor and an immune checkpoint inhibitor," said Choueiri. The CLEAR study is the last of the clinical trials launched to compare immunotherapy and targeted drug combinations to sunitinib, and sunitinib will not be the comparator drug in future studies because the combinations have been shown to be superior in these advanced kidney cancer patients, said Choueiri.
Almost all patients in the CLEAR study experienced some adverse events during treatment. The most common adverse events were diarrhea and high blood pressure. These side effects resulted in treatment discontinuation in 37.2% of patients in the lenvatinib / pembrolizumab group and a dose reduction of lenvatinib in 68.5% of patients. "Although the combination of lenvatinib and pembrolizumab was associated with some notable side effects, these adverse events are often adequately managed," the researchers said.
The drug combination could become a new standard treatment for advanced kidney cancer
Robert Motzer et al., Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma, New England Journal of Medicine (2021). DOI: 10.1056 / NEJMoa2035716
Dana-Farber Cancer Institute
Immunotherapy – targeted combination of active ingredients improves survival in advanced kidney cancer (2021, February 13)
accessed on February 14, 2021
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