A rare case of the Food and Drug Administration deciding to override one of advisory panels occurred yesterday, as the agency approved Eli Lilly’s Gemzar for recurrent ovarian cancer.
Chances of Gemzar (gemcitabine) having its indications extended to include the new use seemed vanishingly small back in March, when the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted nine to two against approval on the grounds that adding Gemzar to standard treatment with carboplatin had not increased overall survival.
The panellists were particularly concerned that, in approving the drug, the FDA would be giving the go-ahead to first-line use of Gemzar in recurrent disease, without sufficient data to prove its efficacy.
But the agency has decided that Gemzar plus carboplatin is an effective regimen for women with advanced ovarian cancer who have relapsed at least six months after initial therapy, based on progression-free survival data.
At the heart of the FDA’s decision is that nearly two-thirds of women with ovarian cancer – regardless of the stage at diagnosis – will develop either recurrent or persistent disease and be candidates for second-line therapy.
The agency has been trying to develop guidelines on the best endpoints to select for ovarian cancer studies and appears to have accepted the view that progression-free survival is a suitable surrogate because it avoids the confounding effect of additional treatment and provides a measure of clinical benefit that is predictive of an increase in overall survival. This viewpoint is already becoming established for lung and colon cancers.
Helping women last longer without the need for additional chemotherapy regimens also provides a benefit in terms of avoiding treatment side effects, according to Lilly.
In a 365-patient Phase III trial carried out by the Gynecologic Cancer Intergroup (GCIG) consortium, Gemzar plus carboplatin was found to increase progression-free survival by 48% compared to carboplatin alone. Complete response rates – in other words the total disappearance of the tumour, occurred in 15% of the combination group and 6% of patients on carboplatin alone. Overall survival was 18 months for both groups.
This is the fourth approved indication for Gemzar, which with sales of $1.3 billion in 2005 is Lilly’s second-biggest drug, and the first time that the FDA has approved an ovarian cancer drug based on progression-free survival alone. It is already approved for pancreatic, breast and non-small cell lung cancers.