Immunotherapies: More Options, More Approvals, and More Questions

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By Jennifer King, Director of Science and Research for Lung Cancer Alliance

It has been quite a busy and exciting two weeks for the Food and Drug Administration (FDA) and the lung cancer community!  On October 2, 2015, the FDA approved a new immuno-oncology drug made by Merck called Keytruda (pembrolizumab) for use in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and any appropriate targeted therapies (such as Tarceva or Xalkori) stop working . This drug is the second anti PD-1 inhibitor approved for lung cancer – it is considered a checkpoint inhibitor, which is a type of immunotherapy.  Keytruda is the same type of drug and targets the same pathway as the Bristol Myers-Squibb drug Opdivo (nivolumab).

There were two major differences in this approval compared to the Opdivo approval that I wrote about in March.  Importantly, Keytruda was approved for all NSCLC, including adenocarcinoma, not just for squamous cell carcinoma.  Second, Keytruda was only approved for patients who undergo molecular testing (biomarker testing) and test positive for PD-L1.

Then, last Friday, October 9, another early ruling from the FDA:  the Opdivo approval was expanded for use in all NSCLC (after chemotherapy) just like Keytruda.  I had mentioned in the blog comments that this was likely coming based on scientific data presented at meetings but the community was not expecting it for another few months.  In addition, a new molecular test (biomarker test) was approved for use with Opdivo too.

So what does all of this mean for lung cancer patients?

Generally, this is good news although a lot of questions remain (for everyone, including the doctors and the researchers) about how to best use these drugs and tests.  Here are some important points to understand about where we are now:

  • It is good to have options and the Keytruda approval gives NSCLC patients another drug option
  • Both drugs are now approved for all types of NSCLC after trying other treatments
  • If you test positive for PD-L1 (by either test), you are significantly more likely to respond well to Keytruda or Opdivo. This can help guide your treatment decision. As of this week, both Quest and LabCorp are some of the major diagnostics companies providing both tests.
  • Currently, you are required to take a test to go on Keytruda, but you are not required to take a test to go on Opdivo. This may change, but that’s where we are on 10/15/15.
  • Unlike the molecular tests for targeted therapies (EGFR, ALK), the PD-L1 tests do not seem to be as definitive. Not everyone who tests positive responds to the treatment (45% in the Keytruda study).  There are also people who test negative who do still respond to the immunotherapy drugs, it’s just a much lower percentage of people.  Researchers are still trying to understand this.

As I mentioned, many questions remain for researchers and doctors.  Not only is there no head-to-head study data about which drug is better (the general thought is that they will be similar), but there has also been no head-to-head comparison of the tests.  There are differences between the tests in how many cells have to have PD-L1 to be a “positive”.   Also, although you would suspect that the test associated with Keytruda will also predict response to Opdivo and vice-versa, there have been no studies showing this since each test was created and tested with each specific drug. Lastly, neither drug is currently approved in small cell lung cancer; but there is early data suggesting there may be benefits for those patients too.

The science is going to keep evolving and both Keytruda and Opdivo are in multiple active clinical trials to test earlier rounds of treatment as well as combinations with other types of drugs.  So stay tuned. Hopefully we will keep getting answers to more and more of the questions.


If you fall out of the approval requirements to take either of these drugs, you may be able to receive the drug through a clinical trial.  Find one with our clinical trial matching service.