If it seems like U.S. Food and Drug Administration (FDA) approvals for immunotherapy drugs are happening more frequently lately, that’s because they are—and for many different types and stages of cancer, too.
The number of people able to benefit from immunotherapy drugs like checkpoint inhibitors, which empower the body’s immune system to fight off its own cancer, has been increasing at a rapid pace that some have lauded as “revolution” in cancer treatment. In 2011, only one percent of patients with cancer were eligible to receive checkpoint inhibitors, and today, that number has climbed to 43 percent. (Although while 43 percent of patients are eligible to be treated with these drugs, only 12 percent of people treated with them actually end up seeing their cancers respond).
Read MoreNow this week, that same drug has won FDA approval for a specific type of lung cancer called small cell lung cancer (which is less common but typically more aggressive than its counterpart, non-small cell lung cancer).
It’s important to note that the approval was given for a set of very specific criteria, which make up the approval’s “indication.” The indication for this Keytruda approval outlines:
- That the small cell lung cancer being treated must be in an advanced stage, meaning the cancerous cells have metastasized beyond the lungs
- That the cancer has already been treated with chemotherapy (specifically, platinum-based chemotherapy) along with at least one other type of treatment after the chemotherapy
- That the cancer has progressed even after these treatments
The approval for Keytruda was a “fast-tracked” or “accelerated” approval, which means that it was given the green light to enter the market after positive results from earlier-phase (phase II) clinical trial results, rather than after positive phase III clinical trial results (the usual basis for approval). The drug will still go through testing in phase III now that it has been approved, but the difference is that the population of people with this specific lung cancer will be able to access the drug in the meantime.
While this is good news for those who can access the drug right away rather than wait until it has finished testing in phase III clinical trials, it’s worth remembering that phase II trials are conducted on smaller groups of patients than phase III trials are, and sometimes, the phase III trial results that come out later show that the drug isn’t all it was originally cracked up to be.
This was the case for another immunotherapy drug called Opdivo (nivolumab), that was granted accelerated approval for the same indication as Keytruda (advanced small cell lung cancer after chemotherapy and another treatment) last August. Several months after the approval, the phase III clinical trial results showed that Opdivo did not meet its “primary endpoint,” meaning it missed the mark for effectiveness in overall survival.
There’s no way of knowing whether we will see the same course of action play out with Keytruda, but as of now, researchers are optimistic about the drug’s potential—and so too is the FDA.
The Results That Led to the Approval
The early-phase clinical trial that the FDA considered a promising enough basis to grant Keytruda accelerated approval in small cell lung cancer wasn’t actually one trial, but rather a cluster of trials that were part of an ongoing, multi-center study called KEYNOTE.
In the specific parts of the KEYNOTE study that led to the approval (KEYNOTE-158 and KEYNOTE-028), Keytruda demonstrated an overall response rate of 19 percent (which accounted for a complete response rate of two percent and a partial response rate of seventeen percent). A “response rate” refers to the rate at which a cancer tumor responds to a drug or treatment. There were 107 clinical trial participants enrolled in KEYNOTE-158 and 24 in KEYNOTE-028.
This Isn’t Keytruda’s First Rodeo
Keytruda—or pembrolizumab, its generic name—is an especially promising (and widely applicable, it turns out) immunotherapy drug that has already been FDA-approved for the following cancers (some with additional specifics to their indications):
- Melanoma
- Non-small cell lung cancer
- Head and neck cancer
- Classical Hodgkin Lymphoma
- A specific type of large B-cell lymphoma
- A certain type of urothelial carcinoma (a cancer that usually occurs in the bladder, uterus, or nearby areas)
- Any type of solid cancer tumor that cannot be operated on and is considered to be something called “MSI-high” or “mismatch repair deficient”
- Certain types of gastric cancers
- Certain types of cervical cancers
- Hepatocellular carcinoma (a certain type of liver cancer)
- Merkel cell carcinoma (a type of skin cancer that is not melanoma)
- Renal cell carcinoma (a type of kidney cancer)
The list is actively growing, too; according to a press release from Merck, the pharmaceutical company that makes Keytruda, “There are currently more than 1,000 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient’s likelihood of benefiting from treatment with Keytruda, including exploring several different biomarkers.”
Why Are So Many Patients Eligible, But So Few Respond?
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 bind with other markers found on immune T-cells create signals telling the immune system not to attack.
“It’s a Jedi mind trick that tells the immune system ‘move on by ignoring me,’” Dr. Geoffrey Oxnard, a thoracic oncologist at Dana-Farber Cancer Institute told SurvivorNet in a previous conversation about immunotherapy in lung cancer. “If we block that signal, the immune system wakes up, sees the cancer, and attacks.” Checkpoint inhibitor immunotherapy drugs do exactly that: they block the “don’t attack” signal.
But every cancer is different, and not all tumors have high enough expressions of certain markers—including one called PD-L1—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).
And although the accelerated approval isn’t a guarantee that Keytruda will work for everyone with advanced small cell lung cancer that meets the indicated criteria, it has the potential to save lives immediately.
“Today’s approval in small cell lung cancer demonstrates our commitment to bringing forward new treatment options for patients with advanced, difficult-to-treat cancers,” Dr. Jonathan Cheng, vice president of oncology clinical research in Merck Research Laboratories said in the press release. “We look forward to continuing to advance important clinical research in small cell lung cancer.”
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