In 2018, the FDA approved the combination of 2 immunotherapy drugs as initial treatment for advanced kidney cancer. This regimen is nabulizumab (Ondivolol, Bristol-Myers Squibb) + ipilimumab (Yervoy, Bristol-Myers Squibb).
How does this new regimen work? What kind of patients is it for? We invited Professor Dingwei Ye and Associate Chief Physician Guohai Shi of the Cancer Hospital of Fudan University, the leading experts in this field, to give you an analysis.
Which patients can be considered for the new protocol?
Advanced renal cell carcinoma is very tricky to treat and cannot be cured by surgery or radiation therapy. The majority of kidney cancers are clear cell cancers, and chemotherapy is largely ineffective in these cancers, so targeted agents are being used. Half of the patients who respond well to targeted therapy usually survive for more than 30 months.
But up to 75% of patients do not respond well to targeted therapy and have a much shorter survival. The new regimen, which is “entering” in 2018, is aimed at this group of patients.
What’s so great about this new regimen?
Why did the FDA approve this combination?
Why did the FDA approve this combination? It was based on the results of a phase III study. In this study, the new regimen reduced the risk of death by 37% in patients with “intermediate-to-high risk” advanced kidney cancer, with an objective remission rate of 42%, almost twice that of sunitinib (27%); and 9% of patients achieved complete remission, far more than the 1% with sunitinib.
Is this regimen safe?
In the study mentioned above, the incidence of adverse reactions was similar to sunitinib in patients using the new regimen; however, 22% of patients discontinued because they could not tolerate the toxicity, significantly higher than the 12% for sunitinib; and another 35% of patients had glucocorticoids used by their doctors to control adverse reactions despite not discontinuing the drug.
It is clear that the new regimen still requires vigilance for adverse reactions. In particular, a “black box warning” was added to ipilimumab, one of the most serious forms of FDA warnings for marketed drugs, warning that the drug may cause “lethal immune-mediated adverse reactions,” including small bowel colitis, hepatitis, dermatitis, and neurological problems. The FDA has also issued a warning that the drug may cause “lethal immune-mediated adverse reactions,” including small bowel colitis, hepatitis, dermatitis, neurological and endocrine disorders.
Can Chinese patients use this new regimen?
Can Chinese patients use this new regimen?
As mentioned above, the foreign recommendation is that targeted agents should be preferred for “low-risk” patients, that is, those who respond well to targeted therapy, while the new regimen is preferred for first-line therapy for patients with intermediate to high-risk advanced kidney cancer.
Among them, navulizumab has been marketed in China but is not approved for kidney cancer, and ipilimumab is not yet available in China. Therefore, this new regimen will not be available to domestic patients for a short time.
Extended reading
How do you determine who is at “intermediate to high risk”? According to the commonly used criteria (IMDC criteria), patients are at intermediate to high risk if they meet any 1 of the following 6 criteria: 1) initial treatment <1 year from diagnosis; 2) poor physical status, Karnofsky score <80%; 3) lower than normal hemoglobin; 4) higher than normal platelet count; 5) higher than normal neutrophil count; 6) calcium concentration after correction >10 mg/dL. ;10 mg/dL.
(Note: IMDC criteria, International Metastatic Renal Cell Carcinoma Database Consortium criteria)
If you want to learn more about new drugs coming to market in 2018, click to read