MarylandThe Oncologic Drugs Advisory Committee (ODAC) has essentially
recommended that the US FDA grant accelerated approval to Iressa (gefitinib,
AstraZeneca) for the oral treatment of locally advanced or metastatic
non-small-cell lung cancer (NSCLC) in patients who have previously received
platinum-based chemotherapy regimens.
A senior FDA official said that a decision that data from
the company’s pivotal phase II trial of Iressa are "reasonably likely to
predict clinical benefit" in NSCLC would be "tantamount" to recommending
accelerated approval. The 11-to-3 vote to that effect came despite discussion
of two much larger phase III studies that failed to show improvement in
response rate or survival with Iressa, compared with placebo, when used as
first-line therapy in conjunction with standard chemotherapy regimens.
Iressa is the first of a new class of drugs called epidermal
growth factor receptor-tyrosine kinase inhibitors to come before ODAC. It is a
targeted molecule that attaches to the transmembrane receptors for epidermal
growth factor. In doing so, the drug interrupts the receptor’s signal
transduction pathway, which results in an inhibition of cancer cell
proliferation and an increase in apoptosis.
Should FDA grant accelerated approval to Iressa, Astra-Zeneca
will be obligated to carry out phase IV postmarket-ing studies to confirm the
drug’s efficacy. A key point in the company presentation to ODAC was data that
showed a significant improvement in symptoms. However, prior to their approval
recommendation, ODAC advised FDA by a 9-to-5 vote that symptom improvement
could not be adequately evaluated without a randomized, blinded study. Thus,
FDA could order such a study as a condition of accelerated approval.
Much of the discussion at the meeting reflected on the
unresolved issue within FDA about how to best address the efficacy of targeted
drugs, whose mechanisms of action are quite unlike those of traditional
George Blackledge, MD, PhD, Astra-Zeneca’s vice president of
oncology, addressed the issue immediately, quoting Larry Norton, MD, director
of medical breast oncology, Memorial Sloan-Kettering Cancer Center: "We’ve said
that these new therapies are dramatically unlike chemotherapy, but we’ve tried
to develop them as if they were. Now we know they’re not, and Iressa has to be
used following different paradigms."