ODAC Recommends Non-Small-Cell Lung Cancer Indication for Gemcitabine

The FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended that gemcitabine HCl (Gemzar) be approved both as a single agent and in combination with cisplatin (Platinol) for the treatment of locally advanced or metastatic non-small-cell lung cancer. Gemcitabine is currently indicated for the treatment of locally advanced or metastatic pancreatic cancer.

"Gemcitabine is among the most widely studied agents for the treatment of non-small-cell lung cancer," said Lawrence Einhorn,MD, distinguished professor of medicine at Indiana University School of Medicine, during a presentation before the advisory committee.

The panel’s recommendation, although not binding, will be considered by the FDA in its review of the supplemental new drug application submitted by Eli Lilly in August 1997. The 11-member committee of consultants to the FDA based its recommendation, in part, on data from a randomized, multicenter phase III study that evaluated 522 patients with advanced non-small-cell lung cancer.

Phase III Studies of Gemcitabine Plus Cisplatin

"In a large, multinational phase III study, patients treated with gemcita-bine-cisplatin had a significantly longer survival time, longer time to disease progression, and higher objective tumor response rate than patients treated with cisplatin alone," said Alan Sandier, MD, a lead investigator and assistant professor of medicine at Indiana University School of Medicine.

A second, multinational phase III study compared gemcitabine-cisplatin against cisplatin-etoposide in 133 patients with advanced disease. Median time to disease progression was significantly longer in patients treated with gemcitabine-cisplatin compared with patients who received cisplatin-etoposide. Tumor response rate also was significantly better in patients receiving gemcitabine-cisplatin than in those given cisplatin-etoposide. Although the study was not designed to show a survival advantage, patients who received gemcitabine-cisplatin had a 1-year survival probability comparable to those who received cisplatin-etoposide.

In the combination studies with gemcitabine plus cisplatin, myelosuppression was the most common and most severe side effect reported. Other commonly reported side effects included nausea and vomiting. Patients who received the combination regimen had generally manageable side effects.

Single-Agent Gemcitabine vs Cisplatin-Etoposide

In a third study, single-agent gemcitabine was compared with cisplatin-etoposide among 147 patients. Patients treated with gemcitabine alone showed a tumor response rate and median time to disease progression similar to patients treated with cisplatin-etoposide. Although this trial was not designed to show a survival advantage, patients treated with single-agent gemcitabine had a 1-year survival probability comparable to patients treated with a combination of cisplatin-etoposide.

Myelosuppression and nausea and vomiting were the most common side effects reported.

New Treatment Option

"Recent advancements in chemotherapy have increased survival for lung cancer patients," said Anders Pedersen, md, medical director, Lilly Oncology. "The FDA advisory committee’s favorable review of Gemzar is a step toward giving lung cancer patients a new treatment option to fight their disease."

Lung cancer remains the world’s most prevalent form of cancer and, in the United States, is the leading cause of cancer death among men and women; non-small-cell lung cancer accounts for about 75% of all cases. Among women, reports the American Cancer Society, lung cancer cases have increased 159%.