Pazdur’s smiling face was accompanied by the announcement that, on March 4th, the FDA had rapidly approved Bristol Myers Squib's drug, Opdivo (nivolumab), citing “a dramatic increase in survival in second-line squamous non-small cell lung cancer.”
“The Cancer Letter” characterized the
approval as activism by the FDA, saying that it was an example of the
“extraordinary activist stance” the FDA can take when it sees an advantage in
overall survival. They went so far as to say that the FDA, had “sprung into
action” when they received the clinical trial data, moving toward approval before
the results of the study were even clear to the sponsoring drug company.
It would have been amusing if it
wasn’t so sad.
PD-I inhibitors are a new breed of
therapy that inhibit cancer cells’ ability to evade its host’s immune system. Every
lung cancer specialist in the country has known that PD-1 inhibitors such as
Opdivo are the most important advance in the treatment of advanced non-small
cell lung cancer to come along in 40 years. For the last two years, in fact,
most oncologists have been seeing data on the effectiveness of these drugs presented
at national meetings and widely discussed among investigators.
Some might say defend the FDA by
saying that the food and drug laws require that the FDA determine that a new
drug is both safe and effective before it is approved for general use. True, in
a general sense. But in this case, we know that the two PD-1 inhibitors now in
advanced clinical testing, Opdivo (nivolumab) and Keytruda (pembrolizumab) are
safe. In fact, the FDA said so itself when they approved both drugs for
patients with advanced melanoma. (Though, as usual, they tied doctors’
hands—allowing them to be used only in patients who had failed other therapies and
listing all the prior treatments the patients had to have failed before their
doctors were allowed to use them).
What are the odds that these drugs,
which were deemed safe enough for some patients with advanced cancer, would
have proven to be unsafe in patients with advanced lung cancer? The answer: between
slim and none. In fact, the data show that they are even effective in patients
with poor performance status, i.e. patients who are frail and bedridden, making
them ideal for older and unstable lung cancer patients, especially those who
have smoked.
But the real irony of the FDA
seeing themselves as activists is the failure to approve the drugs for all
subtypes of all non-small cell lung cancer, given that the data show them to be
universally effective. Only 25% of advanced lung cancer patients have the
squamous cell subtype for which the FDA has approved Opdivo. That means the
majority of patients are excluded from this advance.
All lung cancer specialists already
know the PD-1 inhibitors are far better than any existing drug doublet in use
today. If they were approved for all lung cancers today the use of the myriad
of doublets of far more toxic drugs would disappear overnight. In the meantime,
many patients who might benefit from these drugs are getting old hat treatment.
But when the family members and friends of physicians are diagnosed with lung
cancer, these physicians find a way to get the new drugs to them using any
loophole possible.
The FDA will eventually approve
both drugs for all subtypes of advanced lung cancer and even as a first line
treatment. They will have no choice. But they will do it in their own good time.
Meanwhile, thousands of patients with lung cancer will die without the chance
of getting access to these drugs to extend their useful lives. If the FDA really
wants to be considered an activist, they should approve these drugs for all
lung cancer patients now.
-Vincent T. DeVita, MD
