Through the years, we've talked with many patients, sharing what we've learned of immunotherapy. We've observed common misconceptions.
Click on any of the misconceptions below to expand the text:
The treatments for many diseases are established and haven't changed for years. In contrast, cancer treatment is fast-evolving, especially with immunotherapy.
Most oncologists were not trained in immunotherapy, because the advances have been so sudden and recent.
More importantly, the majority of oncologists will follow the "official flowchart" of prescribed treatments. Fears of lawsuits further dissuade them from venturing out of the box with newer therapies.
Oncologists will often prescribe all approved treatments to patients before recommending experimental therapies such as immunotherapy—even if these treatments are less effective or have more side effects.
This is one of the most common misconceptions we've encountered.
Due to the clinical trial process, drugs need to be approved for specific cancers—one at a time. Just because immunotherapy hasn't been approved for your cancer doesn't mean it won't work.
A common refrain we hear patients say is that "immunotherapy is not proven to work for your cancer."
Technically, this is true, until the FDA grants approval. But examining the early "experimental" data may even show results stronger than existing "approved" treatments.
For example, in early 2014 our friend Mary, with refractory Hodgkin's lymphoma, could have taken PD-1 off-label and enjoyed complete remission. We had predicted PD-1 would work for her cancer based on the scientific studies. But her doctor thought it was too experimental.
Instead, she had to endure 9 more months of debilitating chemo and a stem cell transplant. These drugs did absolutely nothing for her disease.
Thankfully, she ultimately received Opdivo (PD-1) off-label and is now tumor-free and back at work.
Two years later, PD-1 was finally approved for her cancer. Only then would oncologists prescribe it to patients. In the interim, many of these patients would not have been given PD-1. They would have died.
If given the choice, would you rather take a powerful chemo drug that has a 60% probability of shrinking your tumors for 4 months, after which, the tumors are known to definitely regrow? Or would you instead choose an immunotherapy that offers a modest 20% probability of shrinking your tumors—but may suppress those tumors for life, potentially curing you?
Secondly, when looking at the side effects, chemo may have a 50% probability of serious side effects. In contrast, immunotherapy may have <10% serious side effects.
Thirdly, tumor shrinkage isn't always the best measure of benefit. Overall survival (OS) gives a more accurate picture. For example, many chemo drugs shrink tumors and delay growth by a few months. But the overall survival is unchanged. This suggests that the tumors grow even faster when they return, negating any benefit. These patients might as well have not taken chemo in the first place!
In contrast, overall survival with immunotherapies like PD-1 have proven to be impressive, resulting in rapid approvals for many different types of cancer.
Fourthly, looking only at the 20% rate of tumor shrinkage with immunotherapy may cause you to miss the additional segment of patients with stable disease (for example, another 30% of patients). Although the 30% don't enjoy tumor shrinkage, their life may be prolonged—potentially for many years—often, with very low side effects from immunotherapy.
So you see, patients have to objectively examine these nuances. Unfortunately, many patients have told us that their oncologist never provided clear data to evaluate "experimental" immunotherapy against "proven" chemo. Such was our own personal experience.
Thankfully, with the internet, patients can obtain this information to make informed decisions.
Yes, some patients have experienced serious side effects from immunotherapy. However, when evaluated objectively against the side effects of chemo and many other targeted therapies, the side effects of immunotherapy are generally mild.
The more serious side effects are caused by autoimmunity (when the immune system attacks healthy organs). Thankfully, these can usually be controlled with steroids. Also, steroids do not seem to compromise the ability of the immunotherapy to attack cancer.
To put things into perspective, let's consider a case in point. In October 2015, the FDA approved Opdivo (PD-1) for advanced lung cancer based on a randomized clinical trial pitting PD-1 against standard chemo (Docetaxel). The risk of serious (grade 3-5) side effects with Opdivo was 10.5%. In contrast, the risk of serious side effects with chemo was 54%.
Patients must examine the data objectively for themselves to get a clear picture—especially since immunotherapy is "new" and not all doctors are familiar with it.
In early checkpoint inhibitor (PD-1 and CTLA-4) clinical trials, investigators removed patients when tumors enlarged in the early 2-3 months following treatment. With chemotherapy and other targeted agents, tumor reponses would have been seen by that timeframe.
But immunotherapy takes time to work (e.g. often 2-3 months). And when immune cells attack, tumors can initially swell.
Using traditional criteria to evaluate tumor progression, doctors assumed that tumor enlargement implied treatment failure. But then, they began observing that patients removed from immunotherapy trials later experienced tumor shrinkage—in some cases, complete regression.
Since then, modified criteria have been developed to measure immunotherapy responses. But not all doctors may be aware of these dynamics.
For example, in late 2015, a patient we know was removed from a PD-1 clinical trial because his tumors were still growing at 9 weeks. His less-experienced doctors assumed immunotherapy had failed.
We encouraged the patient to consult a more experienced physician who'd administered hundreds of PD-1 doses in clinical trials. The physician said to wait another 3 weeks. Sure enough, the tumors had started to shrink by week 12.
Unfortunately, the patient had already been removed from the trial and couldn't continue receiving PD-1.
Once you stop chemotherapy or other targeted therapies, the cancer will almost always come back. This is not necessarily the case with immunotherapy!
Unlike chemo, immunotherapy doesn't directly destroy tumors. It seeks to modify the interaction between tumors and our own immune cells.
If you can get your immune system to recognize your cancer and attack it, you may never need to be treated again. You could remain cancer free as your immune system is capable of standing guard against the cancer for a lifetime.
This long-term suppresion has been seen in patients who received Yervoy in 2000. Some of them are now 16 years cancer-free after treatment. Similarly, many of Dr. William Coley's patients lived for decades after one-time treatment with Coley's Toxins.