Iressa Survival Data Adequately Disseminated To Physicians/Patients, Cmte. Says

AstraZeneca communication to physicians/patients on Iressa survival data has been adequate, FDA Oncologic Drugs Advisory Committee says. FDA asks committee to discuss possibility of recommending Genentech/OSI Pharma’s Tarceva as alternative to Iressa in labeling, but committee resists.

AstraZeneca has adequately informed physicians and patients of results of its Iressa confirmatory trial showing a lack of overall survival benefit in the non-small cell lung cancer setting, an FDA advisory committee said March 4.

FDA's Oncologic Drugs Advisory Committee agreed, with one member dissenting, that information disseminated by email, "Dear Doctor" letters, sales reps and to patients and consumer groups had been sufficient to inform those groups of the preliminary data found in the Iressa trial.

Some committee members said they have been "inundated with information."

"I got more notice about this drug than credit card applications," committee member Michael Perry (University of Missouri) said.

The vote on information dissemination was the only one taken by the committee at the meeting.

However, FDA asked committee members' opinion on whether Iressa labeling should recommend initial treatment of non-small cell lung cancer with Genentech/OSI Pharma's Tarceva , which has shown a survival benefit.

Committee Chair Silvana Martino (University of Southern California) resisted a committee discussion on the FDA suggestion about putting a Tarceva recommendation in Iressa labeling.

"Just communicate that there is a problem with [Iressa] and that there are alternatives," Martino said. She said that FDA's suggestion amounted to telling physicians what to do. "How do you sit in my office and look over my shoulder?" Martino asked.

In Phase III data in 731 patients, Tarceva demonstrated a median survival rate of 6.7 months compared to 4.7 months for placebo. Tarceva was approved Nov. 18, 2004 for the treatment of advanced or metastatic refractory non-small cell lung cancer based on the data.

Iressa received accelerated approval in May 2003 for locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies.

The approval was based on data showing a 10.6% average objective tumor response rate without demonstrating a survival benefit. FDA required a confirmatory trial to show a benefit in clinical outcomes such as survival.

AstraZeneca reported in December that preliminary data from the 1,692-patient Iressa Survival Evaluation in Lung cancer trial, Iressa (gefitinib) failed to show a statistically significant survival benefit over placebo in the overall population (median survival time 5.6 months for Iressa versus 5.1 months for placebo) and in patients with adenocarcinoma (6.3 months vs. 5.4 months) (¹ (Also see "Iressa Promotion Halted; AstraZeneca To Highlight Tarceva Survival Benefit" - Pink Sheet, 17 Dec, 2004.)).

AstraZeneca suggested in its presentation that Iressa could be used in subgroups in which the drug has shown some survival benefit - patients who never smoked and Asians. These subgroups made up about 20% each of the trial patient population.

Iressa patients who never smoked experienced an increase in survival compared to placebo patients (Hazard Ratio= 0.67 [0.49,0.91]); there was no difference between treatments (HR=0.93 [0.80,1.07]) for patients who had ever smoked.

Asian patients (excluding Indian origin) showed an increase in survival compared to the placebo patients (HR= 0.66 [0.48, 0.91]). Median survival time in Asians was 9.5 months for Iressa patients compared to 5.5 months for those on placebo.

For patients of any other racial origin there was no difference between treatments (HR=0.93 [0.81, 1.08]).

However, FDA Office of Medical Policy Director Robert Temple maintained there was no justification for the AstraZeneca suggestion that Iressa be used in Asians and non-smokers. Temple said the numbers were small and that while the analysis in non-smokers was prespecified, the Asian analysis was post-hoc.

AstraZeneca said that final data from the ISEL trial will become available in June. FDA Division of Oncologic Drug Products Director Richard Pazdur said that the agency may bring the full dataset to the committee in the future. FDA will also move forward on working on new labeling for Iressa with the company.

FDA did not ask the committee whether Iressa should stay on the market. Under accelerated approval regulations, the agency could rescind approval if it determines that clinical benefit has not been shown.

Several committee members indicated that they would prefer Iressa stay on the market as an alternative even in the face of a lack of overall survival benefit in the confirmatory trial.

- Danielle Foullon