Genentech/OSI's anti-EGFR agent Tarceva is associated with a two-month improvement in survival for refractory non-small cell lung cancer patients, according to pivotal trial data presented at the American Society of Clinical Oncology annual meeting in New Orleans June 7.

A rolling NDA filing for Tarceva (erlotinib) started Jan. 21; the remaining data are expected to be submitted this summer.

The application for full approval will be based on Phase III survival data on the effect of erlotinib in refractory non-small cell lung cancer.

The firms are seeking an indication for treatment of incurable stage IIIB/IV NSCLC in patients who have previously failed standard therapy for advanced metastatic disease.

Genentech and OSI announced April 26 that a placebo-controlled study (protocol BR21) of Tarceva found a survival benefit in patients with relapsed non-small cell lung cancer.

Tarceva's BR21 enrolled 731 patients, with 50% having received one prior regimen and the remainder having received two prior regimens.

Patients receiving Tarceva had a median survival rate of 6.7 months compared to 4.7 months for placebo patients (p=.001).

After one year, 31% of Tarceva patients were alive compared to 22% for placebo.

The objective response rate for Tarceva was 9%, compared to less than 1% for placebo; duration of response for Tarceva and placebo patients was 7.9 months and 3.1 months, respectively.

The most common toxicity seen was rash. However, the investigators noted that both placebo and Tarceva patients who developed rash appeared to improve more than those who did not.

Less than 2% of Tarceva deaths were deemed to be a result of treatment, compared to 1% for placebo.

[Editor's note: A version of this story first appeared in ¹ "The Pink Sheet" DAILY June 8. Visit our website, www.ThePinkSheetDAILY.com, to sign up for a free trial.]

If approved, Tarceva would be the second oral anti-EGFR agent, following AstraZeneca's Iressa (gefitinib), which was granted accelerated approval in May 2003 (² Also see "Iressa Clears FDA: Phase IV Symptom Trial Will Be First Shot At Full Approval" - Pink Sheet, 12 May, 2003., p. 3).

Genentech is looking to Tarceva's survival benefit to differentiate the product from Iressa (³ Also see "Tarceva Survival Benefit Differentiates Oncologic From Iressa – Genentech" - Pink Sheet, 3 May, 2004., p. 12).

At an AstraZeneca-sponsored symposium following ASCO's annual meeting, researchers joked that Iressa and Tarceva are as comparable as Coke and Pepsi.

"At this point, to me they look like very similar drugs," Thomas Lynch, MD, Harvard University, said.

"Maybe there's subtle pharmacologic differences that will make one or the other better in certain settings," Lynch said.

However, "right now, I don't see any glaring differences that would tell me one of them is going to be dramatically different," Lynch concluded.

In the Tarceva study, approximately half of the patients enrolled had adenocarcinoma. Investigators said there were not any statistically significant differences in the effect seen in Japanese and Caucasian patients.

Data from Iressa's IDEAL-1 study indicated an increased treatment response in non-smoking Japanese women with adenocarcinoma.

Researchers at the symposium said recent data suggesting a correlation between an EGFR gene mutation and Iressa treatment response should not preclude the use of anti-EGFR agents in mutation-negative patients (see ⁴ Also see "Iressa Use Should Not Be Limited By EGFR Mutation Testing, Researchers Say" - Pink Sheet, 14 June, 2004. ).

Last year, Tarceva failed to show a survival benefit in two combination therapy studies.

The TRIBUTE study enrolled 1,038 patients, and the Roche-run ex-U.S. TALANT study enrolled 1,200 patients. Neither study achieved its primary endpoint of 25% improvement in survival rate (⁵ Also see "Genentech/OSI Tarceva NDA Filing Will Wait For Phase III Monotherapy Data" - Pink Sheet, 6 October, 2003., p. 38).

Genentech/OSI Tarceva Shows Two-Month Survival Improvement Over Placebo

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