In reviewing this week’s FDA hearing on the drug, Avastin, and its approval for use by patients with breast cancer, there are many different perspectives. As a cancer survivor, a cancer researcher and a practicing cancer physician, I strive to appreciate these different views and understand that, in the end, each constituent is approaching this with sincerity and noble intentions to secure the best approach for any one patient with breast cancer. Based on the testimony given this week, it is humbling to consider this issue as if you are a patient, a pharmaceutical company, an FDA regulator, a provider and a payer.
What might patients think?
If you are facing metastatic breast cancer, a situation with no known cure, you will take what benefit you can get, even if that is only a few months of stable disease (without growing tumors or worsening symptoms). And when faced with a deadly illness, you are willing to take risks; small risks like asymptomatic high blood pressure or protein in the urine, or the ultimate risk of a life-threatening complication from a drug. After all, you are already facing a fatal illness. And you don’t want the judgment of others getting in the way of you and your doctor exploring any option. The lack of Avastin’s FDA approval for a breast cancer indication means its use would be considered ‘off-label’ and many insurance companies would not pay the high cost of Avastin ($8000 per month) for a situation that is outside of an FDA approved use. To you, for practical purposes, the lack of FDA-approval for this indication means you may no longer be able to access this drug. And maybe you are a patient with breast cancer who has already received or are now receiving Avastin, and are doing well, leading you and your doctor to believe that Avastin is directly responsible for this benefit. It’s hard to know for sure if that’s true, but if it is then being forced to stop Avastin could mean that your cancer would once again gain the upper hand.
What might a pharmaceutical company employee think?
Scientists at Genentech spend their careers searching for ways to better treat serious diseases, including breast cancer. If you are one of those scientists, you’ve been seeing clues in the lab, in animal models, and in other human cancers, that have led you and your fellow Genentech employees to direct substantial time, money, effort and passion into the development of the drug, Avastin. When you review results and see cases of patients with breast cancer who, statistically, would be expected to go follow a dismal path, but in observation while treated with Avastin seemed to go down a better path (such as prolonged progression-free survival), you see confirmation that your science has been correct, the drug works for some patients and you believe patients should gain access to give Avastin a try. Of course, you are also part of a business that must pay the bills for past and future drug development by making a profit on drugs sold in the marketplace, and Avastin serves that purpose, too, to the tune of about $7 billion per year. But if you didn’t also believe that the drug had promise to help people, you would not have pursued it this far and it would sit on the shelf next to their hundreds and hundreds of other such compounds abandoned as not likely to be helpful to patients.
What might an FDA regulator think?
The FDA has a responsibility to independently determine if a drug, when used for a given disease (an indication) is safe, is effective and can be produced and delivered to patients with high quality. As a regulator within the FDA, if you find that there is evidence for this, you would approve the drug for sale in the U.S. In the case of Avastin, you and colleagues at the FDA have already determined that the answers to these questions are ‘yes’ for colorectal cancer, lung cancer and kidney cancer. As such, Avastin is today and will tomorrow be sold in the U.S. The current FDA ruling on whether or not there is evidence that Avastin is also safe and effective for the indication of metastatic breast cancer will not change that fact. Avastin will remain approved for other cancers, and will therefore remain on the market and available for use by physicians and their patients. Prescribing a drug for an indication that doesn’t fall within an FDA approval is called ‘off-label’ use, and it is an extremely common practice. Without a breast cancer indication, Genentech would not be allowed to advertise Avastin for breast cancer, but it can still be sold.
What might providers think?
Providers spend their day face-to-face with patients who are in need. If you are a doctor, you must ask, for a given individual, how good of a treatment is Avastin for metastatic breast cancer, and if it is good enough to prescribe to that patient, who will pay for it? In determining if a treatment like Avastin is good, you must weigh its risks and benefits, applied to what you know not just about some population of similar research subjects but about that particular patient sitting in front of you. You are responsible for translating statistics derived from a population of research subjects into expectations for an individual patient in your office. Presenting such statistics is a real challenge, very well described by Stephen Jay Gould in his essay, “The Median Isn’t the Message.”
What might a payer think?
Payers, including individuals, private insurers and government programs like Medicare, have a difficult responsibility to provide care to a population of ‘subscribers’ given a fixed pot of money. If you are a payer, you also must consider safety and efficacy, risk and benefit, and you often rely on independent agents, like the FDA, to help make those assessments. As a payer, your concept of balancing risks and benefits is similar to that of a patient, but you must also include cost as a ‘risk’ and service to your subscribers as a ‘benefit’: Are people demanding a therapy and are they willing to pay higher premiums to get it? Since the vote against FDA-approval for Avastin in breast cancer, Medicare has already come forward to announce that it will continue to pay for Avastin in the treatment of breast cancer.
Overall, the controversy surrounding FDA approval of Avastin for metastatic breast cancer highlights some important challenges in oncology, highlighted by considering all perspectives. It is common sense that for any therapy, a reputable company would only sell, a regulator would only approve, an oncologist would only prescribe, payers would only pay and patients would only take a treatment if the benefit is believed to outweigh the risk for a given individual. Unfortunately, we don’t have the ability to know if a treatment will work for any one individual, or what side effects that treatment will have for that individual. Today, we are stuck looking at populations of many subjects to get a general sense of efficacy and safety. Moving forward, we need to pursue improvements in prediction tools and response indicators, so called biomarkers, to make strides in this process of assessing drugs.
Dr. Hayes-Lattin is LIVESTRONG’s Senior Medical Advisor. He is also Assistant Professor of Medicine in the Hemotology/Oncology Department of Oregon Health and Science University and Associate Professor of Medicine in the Knight Cancer Institute at Oregon Health and Science University.