There is a remarkable change going on in the treatment of cancer, and now there is new evidence that a large number of people may actually be benefitting from what’s been called the immunotherapy revolution.
In the years since 2011, when the first so-called checkpoint inhibitor drug was approved to treat melanoma, finding a way to use the body’s immune system to fight cancer has generated enormous excitement. (Checkpoint inhibitors are one major immunotherapy pathway which researchers and drug companies are employing to fight cancer.)Read More
According to the latest study, the percentage of patients eligible for checkpoint inhibitors has increased to 43% since 2011, and the percent of patients who respond to these drugs rose to 12%.
The study, led by Dr. Alyson Haslam from Oregon Health & Science University, came up with these estimated percentages by pooling together annual data from all FDA-approved checkpoint inhibitors through August 2018.
How Checkpoint Inhibitors Work
Drugs such as ipilimumab, which allow the body’s own immune system to attack cancer cells, have since been lauded as miracle drugs, and have become a beacon of hope. But with that hope comes an important caveat: immunotherapy isn’t for everyone. Checkpoint inhibitors are only approved for a select number of cancers—and even then, within those specific cancers, response rates can be low.
Melanoma and lung cancer were the first two major indications to receive approval for immunotherapy, but clinical trials are now being carried out across many other cancers.
“I have patients where the immune system has cleaned out the cancer, and they remain cancer-free,” Dr. Geoffrey Oxnard, a thoracic oncologist at Dana-Farber Cancer Institute told SurvivorNet. “But the reality is, most patients don’t get that kind of response. For most patients, it doesn’t work, or it doesn’t work well enough.”
In 2011, only 1% of patients with cancer were eligible to receive checkpoint inhibitors, and only 0.14% of patients responded to these drugs.
But things move fast in cancer research, and a remarkable pace of immunotherapy advancements has followed that first approval in 2011.
An Important Study on Checkpoint Inhibitors
With those advancements, eligibility and response rates have increased.
In addition to ipilimumab, immunotherapy drugs included nivolumab, pembrolizumab, atelizumab, avelumab, and durvalumab. Together, these six drugs have been approved to treat 14 different cancers.
“For the first time, we’re getting truly curative therapies in many kinds of diseases,” Dr. Jim Allison, 2018 recipient of the Nobel Prize for Physiology or Medicine and Chair of the MD Anderson Cancer Center Department of Immunology, told SurvivorNet. “And not just in melanoma but in lung cancer, kidney cancer, bladder cancer, Hodgkin’s lymphoma, Merkel cell cancer, head and neck cancer. It goes on and on.”
But while the huge jump in eligibility and response rates published in the JAMA study are encouraging, the caveat remains. The new estimated response rate of 12.46 percent is a far cry from 0.14 percent, but it’s still a small number. And relative to the 1.54 percent to 43.63 percent increase in eligibility rates, it hasn’t quite kept pace. These factors make it important to manage your expectations when it comes to the promise of immunotherapy.
Can I Benefit in My Cancer Journey?
So how do you know if your cancer will fall into that 12.46 percent that responds to checkpoint inhibitors? The short answer is that you won’t know for sure.
“We still don’t have great tools to identify patients who would have long-term responses,” Dr. Vamisidhar Velcheti, the Director of Thoracic Oncology at NYU Perlmutter Cancer Center, told SurvivorNet.
Having said that, there are several signs that doctors look for to predict whether a cancer might respond to checkpoint inhibitors. To recognize these signs, it’s important to understand how checkpoint inhibitors work on a cellular level.
The reason that the body’s immune system doesn’t naturally attack cancer on its own has to do with markers found on cancer cells. These markers, such as PD-L1, bind with other markers found on immune T cells (in PD-L1’s case, that marker is PD-1) to create signals telling the immune system not to attack. A similar response happens with the protein B7, which binds with the CTLA-4 marker.
“It’s a Jedi mind trick that tells the immune system ‘move on by ignoring me,’” Dr. Oxnard explained. “If we block that signal, the immune system wakes up, sees the cancer, and attacks.”
Checkpoint inhibitors do exactly that: they block the “don’t attack” signal.
Which Cancers Are Most Likely to Respond?
But every cancer is different, and not all tumors have high enough expressions of these markers to make checkpoint inhibitors effective. To that end, those cancers with the highest expressions of PD-L1 are more likely to respond (although that response is not guaranteed). This explains why eligibility remains low: most checkpoint inhibitors are FDA-approved to treat cancers that meet a certain threshold of PD-L1 expression.
As researchers identify other markers that function in a similar way, the hope is that they will develop new drugs to block them, and the upward trend that the JAMA study noted will continue to rise.
“It’s not just hype — it’s here to stay,” Dr. Brendon Stiles, Thoracic Surgeon at Weill Cornell Medicine and NewYork-Presbyterian told SurvivorNet in a conversation about the expanded use of immunotherapy for stage three non-small cell lung cancer. “It’s really changed the paradigm.”
With the rapid pace of advancement, it’s important to engage in transparent discussions with multiple doctors about whether your specific cancer may be eligible for—and is likely to respond to—a checkpoint inhibitor.
“If I had any advice following a cancer diagnosis, it would be first to seek out multiple opinions as to the best care,” Dr. Steven Rosenberg, Chief of Surgery at the National Cancer Institute and the pioneer of immunotherapy told SurvivorNet. “Because finding a doctor who is up to the latest of information is important so that you can make the best decision for yourself in consultation with your care providers.”