Most patients eligible for cancer immunotherapy start treatment within a few months of the medications’ approval by the U.S. Food and Drug Administration (FDA), a new study reports. The results indicate that cancer immunotherapies are adopted much more quickly than is standard practice for newly approved medical treatments, the researchers said.
However, data also shows that participants in clinical trials do not accurately reflect patients treated in everyday practice, which could lead to bias in trial results.
The research, “Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials,” appeared in the journal JAMA Oncology.
Cancer treatment with immune checkpoint inhibitors — medications that take the brakes off the immune system — has led to marked responses in patients with advanced disease.
Although the FDA is accelerating the approval of new treatments — including immune checkpoint inhibitors targeting either the PD-1 protein on immune cells or PD-L1 on cancer cells — there is little information about how quickly these therapies are accessible to patients or whether these patients differ from those participating in clinical trials that result in FDA approvals.
To address these gaps, researchers from Yale School of Medicine collaborated with healthcare software and services company Flatiron Health on a retrospective study of patients receiving cancer treatment from January 2011 through August 2016.
The patients were eligible for treatment with Opdivo (nivolumab) or Keytruda (pembrolizumab), and had either melanoma, non–small cell lung cancer (NSCLC), or renal cell carcinoma (RCC).
A total 3,089 patients (1,742 men and 1,347 women) were in the study. Their mean age was 66 for melanoma and RCC, and 67 for NSCLC.
Results showed that 68.7% of the patients received anti-PD-1 treatment within four months of FDA approval. The rates were particularly high for those with melanoma (79.1%), followed by RCC (71.2%) and NSCLC (65.6%).
At nine months after approval, the proportions of older and younger patients receiving this type of treatment were similar.
However, people treated in clinical practice were significantly older than those in clinical trials that led to the treatments’ approvals. Most given anti-PD1 treatment after approval were 65 and older; those in clinical studies ranged from the late 50s to early 60s.
As it is unclear whether patients in practice respond in the same way as trial participants, this finding supports the importance of studying real-world populations, the researchers said.
“Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials,” they wrote.
“There are many reasons to be excited about the rapid adoption of these new treatments,” Jeremy O’Connor, MD, the study’s first author, said in a press release. “But it can be risky for rapid adoption to be based on early findings from trials because drugs might be shown in later trials to be less effective or even harmful.”
O’Connor said that to prevent the risks of rapid adoption of new treatments, the FDA must use strong evidence and clinical trials must include patient groups that better reflect those in everyday practice.
“Our findings underscore the importance of a thorough FDA review of new cancer therapies,” Cary Gross, MD, the study’s senior author, said.
Although Gross noted that “the standard of care can change virtually overnight, when a new drug is brought to market,” care should be taken that its approval is not based on small studies, those that do not compare the proposed treatment with existing alternatives, or those with an atypical patient population. “[I]t is essential that we think of FDA approval as one step in the continuing evaluation of whether new drugs are indeed beneficial in the larger population.”