Immunotherapy - Hope or Hype?
Inconvenient Truths about Immunotherapy for Advanced Cancer
The most common class of immunotherapy drugs, the checkpoint inhibitors, have revolutionised the treatment of many cancers. Some patients with metastatic melanoma & non-small cell lung cancer have achieved long-term, durable remissions when most would have died within 1-2 years.
This was impossible prior to immunotherapy. One of these drugs, Pembrolizumab (trade name Keytruda), was the first cancer drug to be FDA-approved for a particular genetic change in a tumor, called microsatellite instability, no matter what type of cancer it is.
Few people actually benefit from ‘breakthrough’ cancer immunotherapy:
People with cancer face many challenges, including the symptoms of the disease, the toxicity of the treatment, financial costs, and social expectations. Here’s a new threat: navigating their care in an ocean of hype.
Cancer drugs are all too often hailed as miracles, breakthroughs, game-changers, or even cures, even when they are no such thing. We recently reported in JAMA Oncology that these words were used 50 percent of the time to describe drugs not approved by the FDA, and 14 percent of the time to describe drugs that had only worked in mice. The leap from helping a mouse to saving a human is uncertain, long, and overwhelmingly unsuccessful. Nathan Gay, MD – oncology fellow at Oregon Health & Science University. Vinay Prasad, MD – assistant professor – Hematology Oncology at Oregon Health & Science University
The lesser known Truth that Academia & the Media fail to address:
By Suneel Kamath, MD Despite breakthroughs, the limitations of immunotherapy have been grossly understated in the academic community and mainstream media. The most important limitation is that most patients with advanced cancers will derive zero benefits from immunotherapy.
The reality is, only a few cancers rely heavily on a “stealth mode” to hide from the immune system to survive. The vast majority of advanced colon, breast, prostate, pancreas, or liver cancers are not susceptible to the immune system at all.
An analysis by Drs. Nathan Gay and Vinay Prasad showed that more than 90% of patients with advanced cancers will have no benefit from immunotherapy.
When immunotherapy works, the result is terrific, even life-changing. Today, though, only a tiny minority of patients expected to die from cancer will benefit from immunotherapy. As is often the case, hype sadly exceeds evidence, creating misunderstandings between patients and their doctors.
Although immunotherapies have been used for a hundred years, such as the deliberate injection of bacteria into the body to stimulate the immune system, 2011 marked the approval of the first immunotherapy for cancer, a so-called checkpoint inhibitor named ipilimumab (Yervoy). This class of drugs unleashes the body’s immune system against cancer, and is the subject of much enthusiasm.
SOME SIDE EFFECTS OF DRUG BASED IMMUNOTHERAPIES
While the euphoria continues to grip oncologists in Australia and New Zealand, the euphoric dust has settled in the USA & Europe where they are now treating these new drugs with CAUTION.
Warnings are appearing in the medical literature detailing severe & unpredictable side effects caused by genetically engineered drug based immune therapies. Deaths have been reported & long-term (unpredictable) side effects have been severe. Drs have been told to issue patients with medical alert cards in case they end up in intensive care or emergency wards.
The toxicities of immunotherapy are better than chemotherapy, but are they that much better?
Suneel Kamath, MD “Immunotherapy can certainly be less toxic than most chemotherapy regimens, but in some ways, the side effects are different, rather than better.
Immunotherapy doesn’t just stimulate the immune system to attack cancer cells, but any kind of cell. Most commonly, this presents as inflammation of the intestines, skin, lungs, liver, or glands like the thyroid gland. This can cause severe diarrhea, rash, fatigue, and shortness of breath.
About 20-25% of patients receiving a single immunotherapy drug will experience serious side effects. In a study published in the New England Journal of Medicine combining two similar immunotherapy drugs to treat melanoma, an impressive 57% of patients saw their cancers shrink, but 55% experienced severe side effects.
Thirty-six percent (36%) of patients had to stop their treatment as a result.
Many would argue that we must accept using toxic drugs to treat cancer because it is so life-threatening and difficult to treat. However, there are many other diseases like end-stage heart failure, advanced cirrhosis of the liver that have equally poor prognoses and limited treatment options, yet we don’t use extremely toxic drugs for those diseases.
The difference in oncology is we have a long history of using toxic chemotherapy, which became the frame of reference for both doctors and the general public. New cancer drugs only have to be more tolerable than chemotherapy, a low bar. Our goal should be to find drugs that are not just effective, but safe and tolerable, too.”
Drs. Nathan Gay and Vinay Prasad asked, of all patients dying of cancer in America this year, how many might benefit from a checkpoint inhibitor drug? The answer was just 8 percent.
What do these results mean?
When immunotherapy works, there is no argument — the results are terrific. Patients with otherwise life-threatening cancers live far longer than expected and some may even be cured. But at least today, few patients can expect to be among the lucky ones.
Some argue that these drugs will be approved for more cancers in the years to come, or that they may work better in combination with other drugs or one another. While we hope that comes true, it is not the reality today.
And for several common cancers, like colon and breast cancer, we already know that these drugs work poorly — there is a reason why the first approvals were in cancers like melanoma — and we fear the percentage of people benefiting from cancer immunotherapy will not change greatly.
Who is to blame for the disconnect between reality and hype? All of us. Doctors, researchers, the pharmaceutical industry, reporters, patient advocates — all use sensational language to describe these drugs. To make matters worse, the United States is one of the only countries to permit direct-to-consumer advertising, resulting in an astonishing 80 drug ads airing every hour — some of which are misleading.
We owe it to people with cancer to do better. Navigating the waters of accurate information and reasonable hope is a big challenge for oncology. Deciding when and how to treat cancer is a sacred journey that patients and their doctors make together. Distorting the effectiveness of treatments in the public eye can tear the very fabric that unites patients and doctors. Misunderstanding ensues. Expectations become disappointments. A good death becomes a bad one.
So how did the hype around immunotherapy get started?
Society has an insatiable hunger for hope when it comes to cancer. After decades of relatively small, incremental steps forward, immunotherapy arrived and brought a tremendous amount of hope with it.
The human mind tends to conflate how much it hopes for something to be true with the actual probability that it will become true.
In this case, we all hope immunotherapy will eradicate everyone’s cancer and, as a result, we overestimate the likelihood that cures will occur.
The media and pharmaceutical company advertisements have only fanned these flames.
Happily there is some good news about immunotherapy
For many years, Grace Gawler has referred patients to a little known form of immunotherapy in Japan with most experiencing outstanding outcomes.
Its cell-based (not drug-based) immunotherapy and it’s safe. It’s been used with over 10,000 patients since the 1900s. It is highly effective, predictable, measurable & has no side effects.