FDA: DOUBTS ABOUT LILLY'S PROPOSED OVARIAN CANCER TREATMENT
When taken in combination with a chemotherapy agent, Eli Lilly's cancer drug Gemzar does not improve overall survival for patients with advanced ovarian cancer, said FDA reviewers in documents released prior to an agency advisory committee meeting. They also noted that the combination exposes patients to additional toxicity.
The FDA's Oncologic Drugs Advisory Committee will discuss Lilly's proposed indication for Gemzar (gemcitabine HCl) injection plus carboplatin at its recent meeting. Lilly is seeking approval of the combination to treat advanced ovarian cancer that has recurred at least six months after completion of platinum-based therapy.
The Gemzar-carboplatin combination adds 2.8 months to median progression-free survival (PFS) -- the time during which the progression of a disease is arrested -- FDA reviewers noted in a briefing document. Increased toxicity includes anemia [shortage of red blood cells], neutropenia [abnormally low count of certain white blood cells, or neutrophils] and thrombocytopenia [low platelet count] -- requiring increased red blood cell and platelet transfusions, as well as increased use of granulocyte stimulating factors and erythropoietic agents, the reviewers added.
"The main issue is whether adding 2.8 months to median PFS at a cost of additional toxicity with no apparent effect on survival is a sufficient basis for Gemzar approval for this use," the document said.
FDA reviewers also pointed to an international gynecology organization's concurrence that, in the setting of second-line chemotherapy for advanced ovarian cancer, "progression-free survival does not seem to be a good surrogate for survival." That unanimous recommendation came from a 2004 conference on ovarian cancer, which included member organizations from multiple countries.
"Progression-free survival data remain of interest but are unlikely to be sufficiently persuasive to shift practice patterns," the FDA said, citing the conference's conclusion.
In its background documents, Lilly said Gemzar plus carboplatin offers patients "clinically significant and statistically persuasive improvements" in PFS. The data show a 28 percent reduced risk of progression, the firm said. "The median [PFS] on the Gemzar plus carboplatin arm was 8.6 months compared with 5.8 months for carboplatin treatment, representing a 48 percent increase in median [PFS] for Gemzar plus carboplatin treated patients," the firm said.
The firm also noted that improvement in PFS allowed patients to "maintain a longer period without a decline in quality of life (QoL) and a longer time without the need for further treatment to control disease."
For more information, go to http://www.fda.gov/oc/advisory/accalendar/2006/cder12542d031506.html (http://www.fda.gov/oc/advisory/accalendar/2006/cder12542d031506.html).