Immunotherapy -- targeted drug combination improves survival in advanced kidney cancer

February 13, 2021

BOSTON - Patients with advanced kidney cancer, who received a targeted drug combined with a checkpoint-blocker immunotherapy agent had longer survival than patients treated with the standard targeted drug, said an investigator from Dana-Farber Cancer Institute, reporting results from a phase 3 clinical trial.

The survival benefit demonstrates that an immune checkpoint inhibitor together with a targeted kinase inhibitor drug "is important in the first-line treatment of patients with advanced renal cell carcinoma," said the authors of a study published in The New England Journal of Medicine today and simultaneously presented during American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancers Symposium. The senior author is Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber.

The phase 3 CLEAR study results showed significant benefits from the combination comprised of lenvatinib, an oral kinase inhibitor that targets proteins involved in the formation of blood vessels supplying a tumor, and pembrolizumab, a checkpoint inhibitor given by infusion that helps the immune system attack the cancer. Another group of patients received a combination of lenvatinib and everolimus, a drug that targets a protein, mTOR.

The comparison drug was sunitinib, an inhibitor that targets multiple kinases and has been the standard treatment in these patients with advanced kidney cancer, which carries a poor prognosis. However, standard-of-care 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 achieved improved outcomes for advanced kidney cancer patients compared with sunitinib.

The results of the CLEAR study showed that those receiving the combination of lenvatinib and pembrolizumab not only had longer overall survival but also longer progression-free survival - the period before their disease worsened - 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 following sunitinib treatment.

The primary endpoint of the trial was progression-free survival (PFS). Both combinations proved superior to sunitinib alone: lenvatinib/pembrolizumab achieved a median PFS of 23.9 months vs 9.2 for sunitinib; PFS for lenvatinib/everolimus was 14.7 months.

The 24-month overall survival rate was 79.2% with lenvatinib/pembrolizumab, 66.1% with lenvatinib/everolimus, and 70.4% with sunitinib.

The confirmed objective response rate (percentage of patients whose disease shrank) was 71% with lenvatinib/pembrolizumab, 53.5% with lenvatinib/everolimus, and 35.1% with sunitinib. The rate of complete responses - 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.

"The rate of responses and complete responses, and the progression-free survival were the longest we have seen to date in a phase 3 combination of a targeted VEGF inhibitor and an immune checkpoint inhibitor," said Choueiri. The CLEAR trial is the last of the clinical trials that were launched to compare immunotherapy and targeted drug combinations to sunitinib, and sunitinib will not be the comparison drug in future trials because the combinations have proven superior in these advanced kidney cancer patients, said Choueiri.

Almost all patients in the CLEAR trial experienced some adverse events from treatment. The most frequent adverse events were diarrhea and hypertension. These side effects led to stopping the treatment in 37.2% of patients in the lenvatinib/pembrolizumab group, and 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.
-end-
The study was sponsored by Eisai, Inc., the discoverer of lenvatinib, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Choueiri is supported in part by the Jerome and Nancy Kohlberg Chair at Harvard Medical School. Choueiri's disclosures include receiving institutional research funds from AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Takeda as well as a consulting or advisory role for AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group.

About Dana-Farber Cancer Institute

Dana-Farber Cancer Institute is one of the world's leading centers of cancer research and treatment. Dana-Farber's mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. We provide the latest treatments in cancer for adults through Dana-Farber/Brigham and Women's Cancer Center and for children through Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 10 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care. As a global leader in oncology, Dana-Farber is dedicated to a unique and equal balance between cancer research and care, translating the results of discovery into new treatments for patients locally and around the world, offering more than 1,100 clinical trials.

Dana-Farber Cancer Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.