Our take on "The Death of Cancer" by Vincent T DeVita Jr M.D., and Elizabeth DeVita-Raeburn
In The Death of Cancer, Dr. Vincent DeVita argues that while cancer patients want and deserve additional treatment options, it is often difficult for them to get promising new therapies. GlobalCures, a non-profit medical research organization, was established to help patients access scientifically promising treatments that could be available to them today, so we were very interested to read DeVita’s new book.
DeVita is uniquely qualified to tackle this important topic. He spent his career developing new cancer treatments (including a cure for Hodgkin’s lymphoma) and fighting for his patients, his friends, and, ultimately, himself, to gain access to treatments that were not standard of care. He is currently a professor at the Yale School of Medicine and was previously director of the National Cancer Institute (NCI), physician in chief at Memorial Sloan Kettering Cancer Center, director of the Yale Cancer Center, and president of the American Cancer Society.
DeVita argues that we have finally reached a critical mass of knowledge about cancer and how to eradicate or at least control it, and we have drugs that can target the “hallmarks of cancer” (the different processes that control cancer progression). He stresses the importance of developing combination therapies that affect multiple hallmarks of cancer. The urgent task before us is to rapidly refine treatment protocols so patients can more quickly and easily access and benefit from them. However, current regulations are too restrictive and do not allow for the flexibility that is needed to evaluate the large number of possible combinations. This unnecessarily adds many additional years of testing to the drug approval process.
DeVita discusses the struggles to gain access to scientifically promising cancer therapies that are not yet part of standard of care, including political and financial challenges. The Death of Cancer focuses on one class of promising therapies – novel drugs that are not yet FDA approved. It is very difficult for patients to get non-FDA approved drugs outside of clinical trials. The current means by which patients may access these drugs is hampered by a long, laborious, and highly regulated process based on individual “treatment INDs” (Investigational New Drug applications, known as “compassionate use”). DeVita advocates for a different approach, such as the one in place for a short time in the early 1980s before treatment INDs, whereby cancer patients were able to easily access some of these drugs through the NCI’s Group C drug distribution program. He feels that it was wrong for this program to be suspended because the treatment IND process does not work for cancer. A new law called the “right to try” aims to allow terminally ill patients faster access to some experimental drugs, though it is unclear how many patients it will help.
The question of when and how experimental treatments should be available to patients is a difficult one, because the regulations are in place to protect patients against potentially toxic therapies that also may not provide a therapeutic benefit. GlobalCures has identified one solution to this problem, which is to develop new cancer treatments based on drugs that have been around for a long time and are known to have little toxicity.
Where GlobalCures comes in
DeVita focuses on therapies that are not yet FDA approved. A different class of promising therapies, which should be much easier for patients to get, is drugs that are already FDA approved for non-cancer indications that could be repurposed to treat cancer. GlobalCures focuses on these drugs, and, in particular, those whose patents have expired and are now inexpensive generics. New uses for old drugs are continually being discovered based on our evolving understanding of cancer and ability to perform in silico and in vitro screens and retrospective analyses. Their safety profiles are established, and many have little toxicity. Though not widely known, some have already shown efficacy for cancer in Phase II clinical trials. The treatments could be immediately available to patients since the use of approved drugs “off-label” as part of medical practice is legal and does not require an IND.
GlobalCures has aggregated and vetted data from thousands of studies (primarily from published literature) to create a database of more than 50 such repurposing opportunities. These treatments target the same pathways that are being pursued by pharmaceutical companies; many are immunotherapies. We are now identifying the most promising combinations for different types of cancer. Surprisingly, even these treatments are difficult for patients to access for a number of reasons.
The primary reason why they are not offered to patients is that they haven’t yet been proven effective for treating cancer in large randomized Phase III clinical trials and, therefore, are not part of standard of care for cancer. We refer to these treatments as “financial orphans” because the trials are very expensive (typically over $10 million each), and there’s no financial incentive for pharmaceutical companies to pay for them since new use patents are not possible or enforceable. Therefore, companies would be unable to recoup the development costs with drug sales for the new use. Government and cancer foundations typically do not fund Phase III clinical trials. Thus, despite great promise, there is a funding gap for these studies. Without definitive Phase III trials, their efficacy for treating cancer as well as potential side effects, particularly in the case of combination therapy, remains in doubt. As a result, most doctors will not be aware of these options or be comfortable offering them to patients, and insurance companies are unlikely to cover the costs. GlobalCures is facilitating clinical trials for the most promising repurposed drugs, including identifying study staff and funding.
As DeVita points out, testing combination therapies within our current clinical trial system will take a long time. Many cancer patients understand that these treatments may not be effective and may have some unknown side effects, and they are willing to take those risks to try the treatments now. We often hear this from patients who have a poor prognosis and have exhausted all other options. They do not have the time to wait for clinical trials to be completed. While DeVita might support these patients and the use of financial orphans off-label, most doctors will not.
Why are doctors reluctant to support off-label use? When doctors deviate from standard of care, they risk litigation as well as possible peer/institutional disapproval (issues that DeVita discusses at length in his book). They are generally unaware of all the existing data, buried in published literature that they do not have time to scour and pursue, so they are unsure how to prioritize such approaches. They may be hesitant to administer treatments that are typically prescribed by non-oncologists (e.g., anti-malarial, anti-fungal, and diabetes drugs). Finally, they may have to spend time convincing insurance companies to pay for the treatments, or else patients would be responsible for the costs. GlobalCures is helping patients access these promising treatments now by raising awareness about the existing data and tracking outcomes from off-label use to learn from n-of-1 experiences.
Cancer patients have a reason to be optimistic. Deaths due to cancer have declined 25% over the last 25 years, and DeVita believes that we can now cure the remaining cancers, or at least convert them into chronic diseases. But to do so will require new approaches, such as the use of repurposed generics, which are uniquely promising and largely untapped opportunities that could quickly improve patient outcomes and reduce cancer healthcare costs. The recent success of immunotherapies, rapidly escalating cancer treatment costs, and growing recognition of the importance of combination therapies all call for a dedicated effort to validate these available drugs as cancer treatments.
“We are not limited by the science; we are limited by our ability to make good use of the information and treatments we already have,” DeVita writes. “We are depriving cancer patients of what they – and their families – want most. A chance. We are losing too many people who should not be lost.” We wholeheartedly agree.