The METEOR study, among other new clinical trials testing a group of new drugs that treat renal cell cancer, has shown significant improvements to survival rate for patients with advanced tumor growth.
The New England Journal of Medicine has published two papers outlining different kidney cancer treatments that will be presented along with the findings of new studies at the European Cancer Congress in Vienna, Austria. According to a report from Forbes, each of the studies shows a significant benefit for a new medication for patients suffering from advanced refractory renal cell tumors.
The first study shows how an immune checkpoint antibody called nivolumab, or Opdivo, increased the chances of overall survival from renal cell cancer. It is the first phase 3 study to show this much improvement in treating advanced kidney cancer. The medication also improved the quality of life in patients suffering from renal cell tumors.
The second study examined the effects of a pill called cabozantinib, or Cometriq. It was shown to hinder the growth of tumors in the kidney, and an editorial that accompanies the study says that the benefit of taking each drug is “unequivocal,” but it also highlights some of the drugs’ limitations, a major one being the cost of each.
When taken together, the studies’ findings can have serious implications for cancer patients suffering from renal cell tumors in the advanced stages. The research offers new insights into treatment strategies and potential expenses for testing and prescribing new medications that target the immune system with antibodies. They stand to help patients not only suffering from advanced kidney cancer, but from other types of tumors as well.
The METEOR study compared the benefits of two pills, cabozantinib and everolimus. In a sample of 658 patients, all suffering from renal cell cancer with tumors that had progressed after undergoing a therapy that targets VEGFR. The open-label randomized trial showed that people taking cabozantinib for a window of roughly eight months were twice as likely to survive without further progression of their cancer than they were from taking everolimus.
The study was funded by the company Exelixis Inc, which manufactures cabozantinib under the name Cometriq. The oval-shaped drug is a small-molecule medication that helps prevent the spread of tumors by blocking VEGFR and other tyrosine kinases including Met and Axl in the body. It was approved by the FDA for the use in treating cancer in the medullary thyroid, but the recent study suggests that it may be a useful treatment for kidney cancer as well.
The other study, named CheckMate 025, compared nivolumab, a drug that blocks the PD-1 antibody, and the other oral drug, everolimus. The antibody belongs to a new class of drugs known as immune checkpoint inhibitors. The trial followed 821 adults that suffered from advanced renal cancer of the clear cell variety, which is by far the most common form that people can suffer from. The median overall survival rate for patients randomly selected to receive a treatment consisting of nivolumab was 25 months, while the median overall survival rate for participants receiving everolmus was just 19.6 months. However, the total objective response rate to nivolumab was a mere 25 percent. Complete responses to the drug were even lower at 1 percent. The study received support by Bristol-Myers Squibb, the company that manufactures nivolumab under the name Opdivo.
Each of the new studies compared the new medication in question to the standard treatment for advanced renal cell cancer – everolimus administered at a dose of 10mg taken by mouth each day. This drug, sold by Novartis as Afinitor, is approved by the FDA for treatment of advanced renal cell cancer and various other types of cancer. Typically, the measurable response rate to this drug, an mTOR inhibitor, is extremely low in patients whose advanced forms of cancer didn’t respond well to other targeted treatments, usually less than just 5 percent. It is also associated with cases of toxicity. Side effects to the treatment can include a rash and other allergic reactions that lead to symptoms including chest pain, difficulty breathing, jaundice, fever, sores, bleeding and other health issues.
The studies had a hard time predicting the response rate in patients taking nivolumab based on pathological features of the tumors, like their levels of PDL-1. The antibody was administered intravenously to patients every other week. Nivolumab patients experienced slightly lower levels of toxicity; only four different adverse side effects were reported in 19 percent of the study group, compared to the 37 percent of patients who took everolimus. No deaths in the study were linked to the use of nivolumab, and side effects were generally less severe. They included fatigue, nausea, and itching, and in rare cases low blood counts such as anemia.
Randomization in the CheckMate 025 trial ended in July this year so that doctors could assess the survival benefits of nivolumab. The drug improved the quality of life in more patients that the everolimus group.
According to Dr. Robert Motzer, a kidney cancer specialist from Memorial Sloan Kettering Cancer Center in New York City, and a principal investigator in each of the studies, “These are exciting results. One of the challenges in kidney cancer is that patients develop resistance to treatment. There is a need for new medications.” Dr. Motzer received funding for the studies through MSK Cancer Center and from both companies that manufacture the drugs, BMS and Exelixis. He also serves as a consultant for Pfizer, Novartis, and Eisai.
The study examining nivolumab was the first that proved how immune checkpoint inhibitors could improve the quality of life in people that suffer from kidney cancer. The drug was significantly less toxic than everolimus, and showed improved overall survival and durable responses. It was clearly the safer and more reliable choice.
With cabozantinib, the greatest benefit revealed by the study was its increased rate of progression free survival. The METEOR study, which was an open-label phase 3 analysis as well, showed that the total objective response rate for cabozantinib was 21 percent, while it was just 5 percent for everolimus.
“The benefit of cabozantinib may be greater than these numbers suggest, Dr. Motzer said. “The overall survival data are not yet mature. There may be durable responses, but we don’t know that yet.” The METEOR study compared cabozantinib to everolimus in an effort to evaluate the responses from patients with advanced tumors that had resisted treatment up until that point. Motzer said that it could help more patients suffering from these types of cancers, and could even be used in combination with other drugs.
Therapies for advanced kidney cancer have been extremely limited up until this point, and the FDA has only approved about a dozen medications so far. New drugs are grouped into mTOR inhibitors, like evrolimus, and targeted drugs that attack one of several VEGF receptors and other molecules that signal for proteins in cancer growth. “There is along history of treating cancer with immune drugs, but Interferon and IL-2 only helped a small proportion of patients,” Dr. Motzer said.
While cabozantinib was found to be the more toxic of the two new drug choices, Dr. Motzer said that its effects were manageable. Patients that reported toxic side effects were given a reduction in dosage and reported improvement.
Dr. Padmanee Sharma, an oncologist with a PhD in immunology that directs the immunotherapy platform at the MD Anderson Cancer Center in Houston, thinks the study brings us a step closer to coming up with viable treatments for renal cell cancer in the advanced stages. “This is the first time a phase 3 study has ever shown a survival benefit in treatment of patients with advanced kidney cancer,” she said. “This drug gives hope to patients with renal cell cancer. These are not like the drugs cancer patients used to get. You’re not in bed, losing your hair, throwing up.”