Thank you for the opportunity to speak today. My name is Dr. Laura Gottschalk. I received my Ph.D. from Johns Hopkins School of Medicine and previously worked as a cancer researcher. I am speaking today on behalf of the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers, and policy makers. We do not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.
We understand that patients who have T790M positive lung cancer are tired and frustrated because time after time they are given a cancer therapy only to be told that it is not working to treat their cancer. So the promise of a new drug that will successfully treat their specific form of cancer, even down to the exact mutation, can sound very promising. However, based on the data presented today, we think you’ll agree that rociletinib does not meet FDA standards of proven safety or effectiveness.
First, we are concerned with the efficacy of rociletinib. The objective response rate of about 30% does seem promising, but several important caveats need to be kept in mind. Accelerated approval can often lead to more lenient clinical trials, including the single-arm studies used here. We believe that without proper controls, an accurate assessment of rociletinib’s efficacy and safety cannot be made. The surrogate endpoint used for the studies, objective response rate, has in the past been shown to be a poor indicator of cancer drug efficacy. A study from December of last year looked at cancer drugs that were approved by the FDA over a recent 5 years, based on surrogate endpoints. In post-market studies, only 14% of these approved cancer drugs were found to improve patients’ survival. And yet, our Center found that all the unproven cancer drugs were still on the market, many costing more than $100,000 per year. These results show that surrogate endpoints such as objective response rate too often provide false hope while costing patients more they can afford.
In the study of rociletinib, there is also a possible red flag warning: only 1 patient had a complete response out of the 98 patients who actually had an observed response to the drug. This makes it seem unlikely that this drug will be found to be effective in controlled clinical trials. The ongoing randomized phase III trial comparing rociletinib to chemotherapy should give a better idea of overall survival in patients. Until those results are available, the FDA should not approve yet another drug that could easily fail to be effective for T790M patients.
In addition to questioning the efficacy, we are also very concerned with the safety profile. The drug had numerous side effects that would directly decrease a person’s quality of life–diarrhea, fatigue, nausea, and vomiting in approximately half of the patients. Meanwhile, most patients suffered for almost two months before learning that the drug wasn’t working for them. Even more troubling were the high numbers of serious adverse events such as hyperglycemia and QT prolongation. As a result, the side effects resulted in most patients reducing, interrupting, or stopping their dosing completely. Since there was no standardized method for reducing dosage in patients, this makes it difficult to accurately assess the efficacy of rociletinib.
In conclusion, we realize that there is currently an unmet need for a drug to treat patients whose NSCLC has become resistant to first line TKI therapies via the T790M mutation. However, this does not warrant the approval of yet another drug that will not significantly improve outcomes for these patients. Fortunately, there is hope on the horizon, because the preliminary results for osimertinib for the same patients appears to be much more effective with fewer serious side effects.
For rociletinib to be worthy of FDA approval, studies are needed to determine which subgroups of patients are most likely to benefit from treatment and determine how to reduce the number of adverse events experienced by these patients, perhaps by looking at NAT2 status. Additionally, these studies should have the proper control groups and outcome measures to demonstrate effectiveness as measured through clinically relevant endpoints, such as overall survival.
Thank you for your time.