Tarceva..again..
Got this in my mailbox...
To: ASCO membership (domestic USA, embargo date 11/18/04)
From: Richard Pazdur, M.D.
Director, Division of Oncology Drug Products,
Center for Drug Evaluation and Research, FDA
On November 18, 2004 the U. S. Food and Drug Administration approved erlotinib (TarcevaTM tablets, OSI Pharmaceuticals Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
Safety and efficacy were demonstrated in a 731 patient double-blind, multi-national, randomized trial comparing erlotinib 150 mg p.o. daily to placebo. Survival was significantly prolonged on the erlotinib arm with a median overall survival of 6.7 months and 4.7 months in the erlotinib and placebo groups, respectively. The adjusted Hazard Ratio (HR) for death in the erlotinib group relative to the placebo group was 0.73, p = <0.001. Progression-free survival was significantly prolonged on the erlotinib arm with a median PFS of 9.9 weeks vs. 7.9 weeks in erlotinib and placebo groups, respectively. The adjusted HR for progression was 0.59, p < 0.001.
The objective response rate by RECIST in the erlotinib group was 8.9% (95% CI: 6.4 to 12.0%). The median response duration was 34.3 weeks, ranging from 9.7 to 57.6+ weeks. Two responses (0.9%, 95% CI: 0.1 to 3.4) were reported in the placebo group.
An exploratory analysis of Epidermal Growth Factor Receptor (EGFR) protein expression status on treatment survival effect was performed; however, EGFR status was known for only 33% of patients. The EGFR expression was determined using the DAKO EGFR pharmDx(tm) kit. About half of the patients with known EGFR status were positive and half were negative. In the EGFR positive subgroup, erlotinib prolonged survival compared to placebo (median 10.7 vs. 3.8 months, HR=0.65, p=0.033). No apparent erlotinib survival effect was observed in the EGFR negative subgroup (erlotinib median: 5.2 months vs. placebo median: 7.5 months; HR=1.01, p=0.958). However, the confidence intervals for the EGFR positive and negative subgroups are wide and overlap. Thus, an erlotinib survival effect in the EGFR negative subgroup can not be excluded. Post approval clinical trials will prospectively examine the relationship of EGFR status and survival effects.
An additional subgroup survival analysis examining the effect of smoking status showed that the erlotinib survival benefit was greater in patients who had never smoked (HR 0.42; 95% CI: 0.3, 0.6) than in smokers (HR 0.87; 95% CI: 0.7, 1.1).
The most common adverse reactions in patients receiving erlotinib were diarrhea and rash. Grade 3/4 rash and diarrhea occurred in 9% and 6%, respectively. Rash and diarrhea each resulted in study discontinuation in 1% of erlotinib-treated patients. Only 6% and 1% of patients required dose reductions for rash and diarrhea, respectively. The median time to onset of rash was 8 days; the median time to onset of diarrhea was 12 days.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2004/021743lbl.pdf.
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It seems DNA/OSIP taking a beating since they revealed the subset analysis re: EGFR status..
I perused through the label..quite interesting, imo...shame we get this detail only after it's been approved or a product going to ODAC..Interesting drug interactions..
IMHO:[edit: analysts now low-balling estimates..sales to all the institutions running trials are substantive, EGFR testing not feasible for all patients...yet...it's cost/side effect profile is advantageous compared to current 2nd line therapies(Alimta, taxotere, Iressa...which is $1500/mo. vs. $2000 for Tarceva as stated on last night's CC.. The parenterals like Alimta are in the $4-5K range..
FWIW..my first drug approval..using it as a case study..
Zeta |
