Immunotherapy-Targeted Drug Combination Improves Survival of Advanced Renal Cancer

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Researchers at the Dana-Farber Cancer Institute report the results of a phase 3 clinical trial, and patients with advanced kidney cancer who receive targeted drugs in combination with checkpoint blocker immunotherapies are treated with standard targeted drugs He said he had a longer survival than the patients who were treated.

Survival benefits indicate that immune checkpoint and target kinase inhibitors are “important in first-line treatment of patients with advanced renal cell carcinoma.” New England Journal of Medicine It was presented today at the American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancer Symposium. The lead author is Dr. Toni Choeili, MD, director of the Dana-Farber Cancer Urogenital Oncology Center.

The results of the Phase 3 CLEAR trial show that lenvatinib, an oral kinase inhibitor that targets proteins involved in the formation of blood vessels that feed tumors, and pembrolizumab, a checkpoint inhibitor given by infusions that help attack the immune system. Showed great benefits from the combination of. cancer. Another group of patients received a combination of lenvatinib and everolimus, a drug that targets the protein mTOR.

The comparative drug is sunitinib, an inhibitor that targets multiple kinases, and has become the standard of care for patients with advanced renal cancer with a poor prognosis. However, standard treatment options now include treatment with two checkpoint inhibitors or immune checkpoint inhibitors as a combination of checkpoint and kinase inhibitors. These combinations improved outcomes in patients with advanced renal cancer compared to sunitinib.

The results of the CLEAR trial show that patients receiving the combination of lenvatinib and pembrolizumab not only have a longer overall survival, but also a longer progression-free survival (the period before the disease worsens) and a higher response rate. I did. In addition to the combination of lenvatinib and pembrolizumab, clinical trials also tested the combination of lenvatinib and everolimus. It is approved for patients with advanced renal cancer whose disease progresses after sunitinib treatment.

The primary endpoint of the study was progression-free survival (PFS). Both combinations have proven to be superior to sunitinib alone. Lenvatinib / pembrolizumab achieved a median progression-free survival of 23.9 months compared to 9.2 for sunitinib. The Lenvatinib / Everolimus PFS was 14.7 months.

Overall survival at 24 months was 79.2% for lenvatinib / pembrolizumab, 66.1% for lenvatinib / everolimus, and 70.4% for sunitinib.

The confirmed objective response rate (percentage of patients with reduced disease) was 71% with lenvatinib / pembrolizumab, 53.5% with lenvatinib / everolimus, and 35.1% with sunitinib. The complete response rate (total tumor shrinkage) was 16.1% in patients receiving lenvatinib / pembrolizumab, 9.8% in the lenvatinib plus everolimus group, and 4.2% in the sunitinib group.

“Response rate, complete response, and progression-free survival were the longest ever seen in a phase III combination of targeted VEGF and immune checkpoint inhibitors,” said Choueiri. I am. The CLEAR trial is the last clinical trial initiated to compare immunotherapy and targeted drug combinations with sunitinib, and sunitinib has proven to be superior in these patients with advanced kidney cancer. It is not a comparative drug in the test.

Almost all patients in the CLEAR trial experienced some adverse events with treatment. The most frequent adverse events were diarrhea and hypertension. Due to these side effects, treatment was discontinued in 37.2% of patients in the lenvatinib / pembrolizumab group and the dose of lenvatinib was reduced in 68.5% of patients. “The combination of lenvatinib and pembrolizumab was associated with some notable side effects, but these adverse events are often well-managed,” the researchers said.

Drug combinations may become the new standard of care for advanced kidney cancer

For more information:
Robert Motzer et al, lenvatinib and pembrolizumab or everolimus for advanced renal cell carcinoma, New England Journal of Medicine (2021). DOI: 10.1056 / NEJMoa2035716

Provided by Dana-Farber Cancer Institute

Quote: Immunotherapy-Targeted Drug Combination is https: // Advanced Renal Cancer Obtained on February 13, 2021 ( Improves survival rate (February 13, 2021)

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Immunotherapy-Targeted Drug Combination Improves Survival of Advanced Renal Cancer

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