There’s a newfound hope in immunotherapies for cancer, and it’s a drug called nivolumab. On the market under the name “Opdivo,” this checkpoint blockade drug demonstrated a better response rate than other second-line cancer treatments in clinical trials.
Nivolumab works by inhibiting the activity of a protein called PD-1, which is stationed on the surface of T cells and deactivates them, preventing them from fighting cancer in the body. Why would T cells contain this potentially self-destructive surface protein? It’s unclear, but PD-1 activity is only initiated by its ligand, which scientists have found on cancerous cells. In the past, PD-1 activity helped scientists identify the presence of cancer and decide what treatment plan of action to take.
Now with nivolumab in the arsenal of anti-cancer drugs, researchers can prevent able T cells from being held back when the body is trying to fight off cancer. However, a new study from researchers at the University of Texas M.D. Anderson Cancer Center found that nivolumab reduces tumor burden regardless of the biomarker status of patients’ tumors.
"We can get good results without choosing to treat patients based on PD-L1 status," said Padmanee Sharma, MD, PhD. The U.S. Food and Drug Administration has approved nivolumab for advanced melanoma, lung cancer, kidney cancer, and Hodgkin lymphoma.
The clinical trial from the new study included 78 patients with metastatic bladder cancer receiving treatments of nivolumab. Just over six percent of the patients had a complete response to the drug, 18 percent had partial responses where the tumor shrunk by at least 30 percent, and about 28 percent of participants’ tumors remained stable. The approximately 40 percent of participants left showed disease progression.
For the majority (80 percent) of patients, only low-grade side effects existed: fatigue, itching, elevated lipase, rash, nausea, joint pain, anemia. The remaining 20 percent of people experienced more severe side effects, including two participants who opted out of the treatment due to the side effects. Overall, the researchers considered nivolumab to be well-tolerated in this study, especially since bladder cancer patients are frail after an initial treatment of platinum chemotherapy. This is an anti-cancer approach for over half of all cancer types, using platinum-based components that put patients at risk for neurotoxicity.
After 213 days of the clinical trial, 33.3 percent of the original participants were still receiving nivolumab. Almost half of the participants survived at least one year. Although these numbers seem grim, Sharma said it was “better than anything we’ve seen in the past.”
The next step for the researchers behind the clinical trial recently presented at the 2016 American Society of Clinical Oncology Annual Meeting was to combine nivolumab treatment with an immune checkpoint inhibitor called ipilimumab, on the market as “Yervoy.” This drug targets a checkpoint on T cells called CTLA-4, making it both the first ever immune checkpoint inhibitor and the first ever drug to successfully extend the survival of patients with metastatic melanoma.
By comparing the outcomes from the combination treatment with those from nivolumab alone, researchers would know if the additional drug provides more anti-cancer activity. However, the researchers allowed the patients in the nivolumab-only group to start receiving the combination therapy if it showed to be the more promising option for long-lasting health. The findings will be presented later this year.
Source:
ChemoCare,
University of Texas M.D. Anderson Cancer Center
