by Dr. C.H. Weaver M.D. updated 8/2019
CancerConnect News: The Food and Drug Administration granted approvals to Opdivo (nivolumab) and Yervoy (ipilimumab) in combination for the treatment of intermediate or poor risk, previously untreated advanced kidney cancer (renal cell carcinoma) based on the results of the Checkmate 214 clinical trial - longer follow suggests the survival benefit is maintained. (1,2)
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 100,000 deaths worldwide each year. Clear-cell RCC is the most prevalent type of RCC and constitutes 80% to 90% of all cases. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced kidney cancer, is only 12% and new treatments are sorely needed.
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Checkpoint inhibitors are one kind of immunotherapy that has clearly improved the treatment of cancer. Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells.
Checkpoint inhibitors for the treatment of cancer
- Keytruda® (pembrolizumab)
- Opdivo (nivolumab)
- Imfinzi (durvalumab)
- Tecentriq® (atezolizumab)
About Yervoy (ipilimumab)
Yervoy is a monoclonal antibody that targets a molecule known as CTLA4. CTLA4 is found on the surface of T cells and is thought to inhibit immune responses. By targeting this molecule, Yervoy may enhance the immune system’s response against tumor cells. Yervoy was approved in March 2011 for the treatment of melanoma and appears active in a number of cancers.
The current FDA approval for advanced renal cell carcinoma was based on the CheckMate 214 clinical trial that compared the Opdivo and Yervoy combination to Sutent, a standard treatment for advanced renal cell cancer. The combination improved response rates and prolonged survival compared to treatment with Sutent alone.
Follow up data was published in August 2019 with patients on the Checkmate 214 trial now having been followed for an average of 32 months.
Overall 28% of patients treated with the combination survived without cancer progression at 30 months from initiation of treatment compared to only 12% for those treated with Sutent alone.
The adverse event profile was said to be manageable, with no new safety signals emerging.
The most common adverse reactions (reported in at least 20% of patients treated with the combination) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite and no new side effects have emerged as problematic with longer follow up.
“These results show the long-term benefits of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma. The long-term overall survival benefits, high proportions of complete response and ongoing response, and paucity of chronic toxicity with nivolumab plus ipilimumab after extended follow-up compares favorably with available reports of other combination regimens in first-line advanced renal cell carcinoma,” the researchers wrote.
- Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomized, controlled phase 3 trial [published online August 16, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(19)30413-9