Combining an anti-angiogenesis agent, which blocks blood vessel formation, with an immunotherapy agent, was discovered to have promising anti-tumor exercise and no sudden unwanted side effects in an early-phase medical trial in patients with advanced kidney cancer who had not been beforehand handled, in accordance with a researcher on the Georgetown Lombardi Comprehensive Cancer Center who led this research.
The full findings of the research up to now involving the combination of axitinib (Inlyta) and pembrolizumab (Keytruda) will probably be introduced February 10 as a part of the ASCO Genitourinary Cancers Symposium in San Francisco, with context and extra details about the first endpoint to be revealed concurrently in The Lancet Oncology.
Axitinib inhibits angiogenesis, the method of blood vessels forming to feed a tumor. Inlyta was permitted by the U.S. Food and Drug Administration in 2012 for the remedy of patients with advanced kidney cancer after one prior systemic remedy has failed, and has been proven to be selective in the way it works, ensuing in a robust effectiveness to toxicity ratio.
The immunotherapy agent, pembrolizumab, is an immune checkpoint inhibitor that blocks a self-defense mechanism utilized by cancer cells to evade assault and destruction by the physique’s immune cells. It is FDA-approved for the remedy of patients with a number of cancer varieties together with melanoma, lung, bladder and head and neck cancers, however has solely had restricted research in patients with kidney cancer.
Earlier makes an attempt to develop mixtures of anti-angiogenesis brokers and checkpoint-inhibitor-based immunotherapies to deal with patients with advanced kidney cancer resulted in unacceptably excessive ranges of toxicity and thus the mixtures weren’t pursued additional. In distinction, the axitinib-pembrolizumab combination was sufficiently tolerable to allow the brokers to be given at their FDA-approved single-agent dose ranges.
“Our results are unprecedented. The combination doubled the efficacy of the drugs when used alone and the treatment was found to be tolerable,” says Michael B. Atkins, MD, deputy director, Georgetown Lombardi Comprehensive Cancer Center and principal investigator for the research. “Specifically, over 90 percent of patients exhibited tumor shrinkage and the disease was kept under control for a median of over 20 months.”
The investigators began their part I medical trial of this combination in 2014 and enrolled 52 advanced renal cell carcinoma (the most typical type of kidney cancer) patients who had not beforehand been handled for the illness. Their objective was to seek out out what dose of the drug might be tolerated by a subset of 11 patients in the course of the first 6 weeks of the trial, then gauge the effectiveness of the remedy in all 52 patients. All enrollees acquired an intravenous infusion of pembrolizumab initially of the trial after which each three weeks thereafter. Patients additionally took axitinib twice day by day till they might not tolerate the remedy or till no profit was seen. The researchers checked out tumor measurement at trial enrollment, then 12 weeks later and each 6 weeks thereafter.
In the 11-patient subgroup, three of the patients weren’t capable of tolerate axitinib and acquired lower than 75 % of the deliberate dose as a result of toxicities, whereas eight patients skilled manageable unwanted effects, thus establishing this dose degree and the advisable dose degree for additional investigation in a gaggle of 41 further patients. Significantly, patients had fewer liver abnormalities and fewer fatigue than these handled with different comparable combination therapies, Atkins stated. Also, for this new combination remedy, tumor shrinkage or stabilization was higher than that seen in patients taking simply one of many two medicine alone.
Seventy-three % of patients skilled vital tumor shrinkage in response to the combination remedy and the median time in which there was no illness development was 20.three months. Overall survival outcomes are nonetheless incomplete as 88 % of the patients have been nonetheless alive at a minimal 18 months after beginning remedy. By March 2017, 25 patients have been nonetheless being handled, with 22 receiving the drug combination and three receiving pembrolizumab solely.
“A randomized phase III trial comparing our drug combination to the FDA-approved anti-angiogenesis agent sunitinib is underway and it should tell us if this drug combination is better than the previous standard-of-care regimen,” says Atkins. “We think this combination could present a major advance in the treatment of this disease as well as help define effective combinations of similar drugs for other cancers.”
Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Olencki TE, Tarazi JC, Rosbrook B, Fernandez KC, Lechuga M, and Choueiri TK. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion part 1b trial. The Lancet Oncology. Feb. 10, 2018.