Proposed Indication Alimta as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after prior chemotherapy
Study Design One randomized trial comparing treatment with Alimta to treatment with docetaxel 75 mg/2 Stratification factors: P.S.; Disease stage; Number of prior regimens; Response to last prior chemo; prior platinum; prior paclitaxel; baseline homocysteine; treatment site
Docetaxel 2 nd line Survival PtsRRMed (mo) p OS 1 yr (%) p 1 yr DOC 75 vs BSC 55 49 5.5% -- 7.5 4.6 0.0137 12 <0.05 Doc 75 Vs IC (V/I) 125 123 5.7 0.8 5.7 5.6 0.1330 20 0.025
Alimta Administration Alimta 500 mg/m2 IV infusion over 10 minutes on Day 1 of each 21-day cycle. Folic acid 350-1000 mcg daily Vitamin B12 1000 mcg every 3 rd cycle Dexamethasone 4mg po bid days -1, 0, +1 (rash prophylaxis)
Docetaxel Administration Docetaxel 75 mg/m2 as an intravenous infusion over 60 minutes on Day 1 of each 21-day cycle. Dexamethasone 8 mg po bid days -1, 0, +1 (fluid retention & hypersensitivity)
Study Conduct 135 Investigational sites in 23 countries Approximately 21% of the study population came from United States Institutions
Efficacy Conclusions Post-study chemotherapy confounds survival results - 85 (32%) of Alimta pts received post-study docetaxel - Patients who did not receive post-study chemotherapy had shorter survival - 30 more docetaxel treated patients received no post-study chemotherapy compared to Alimta treated patients. - Majority of untreated P-S patients had PS 0-1 Response rates were 9.1% (A) and 8.8% (D)
Safety Conclusions Toxicity spectrum of Docetaxel and Alimta differ. - Docetaxel produces more neutropenia and neutropenic complications (febrile neutropenia, infections, G-CSF use) neurotoxicity, myalgias, alopecia and diarrhea - Alimta produces more thrombocytopenia, skin rash, fatigue, nausea and vomiting, ALT and AST increase, decreased CCr, and weight loss. Folic acid and Vitamin B12 supplements are known to decrease Alimta toxicity. Whether they would also decrease docetaxel toxicity is unknown.