p r i m e l i n e s

Oral Anticoagulant Approved By European Commission
Bayer’s once-daily oral anticoagulant rivaroxaban (Xarelto®), has received final approval from the European Commission for the prevention of DVT and PE in patients undergoing hip or knee replacement surgery. Rivaroxaban, which does not require monitoring of coagulation tests, demonstrated superior efficacy compared to enoxaparin in a pivotal phase III trial.

Can NSCLC Histology Affect Response to Therapy and Overall Survival?
Last month, the United States FDA approved Eli Lilly and Company’s pemetrexed (Alimta®) for use in combination with cisplatin therapy for the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC. The approval was based on the results of a randomized study of 1,725 chemo-naive patients with stage IIIB/IV NSCLC comparing overall survival (OS) after treatment with either pemetrexed + cisplatin (AC) or gemcitabine + cisplatin (GC). Results: median survival (AC 10.3 months vs GC 10.3 months), median PFS (AC 4.8 months vs GC 5.1 months) and overall response (AC 27.1% vs GC 24.7%).

A pre-specified analysis of the impact of NSCLC histology on OS was conducted in this trial and clinically relevant differences according to histology were observed. In the non-squamous cell NSCLC patient subgroup, median survival was 11.0 months in AC and 10.1 months in GC treated groups, but in the squamous cell histology subgroup the median survival was 9.4 months in AC vs 10.8 months in GC treated patients. This unfavorable effect on OS associated with squamous cell histology observed with pemetrexed was also noted in a retrospective analysis of the single agent trial of pemetrexed vs docetaxel in a similar patient population after prior chemotherapy. Current product labeling has been revised to recommend that pemetrexed is also not indicated in patients with squamous cell lung cancer after prior chemotherapy.

These results demonstrate that NSCLC histology can impact treatment outcome and have an unfavorable effect on patients’ overall survival.

Oral TKI Achieves Dramatic Reduction in Risk
of GIST Recurrence
On August 27, 2008 the United States FDA granted priority review status to Novartis’ imatinib mesylate (Glivec®), an oral tyrosine kinase inhibitor (TKI), as the first therapy for adjuvant use after surgery in KIT-positive gastrointestinal stromal tumors (GIST). Similar regulatory submissions have been filed by EMEA and other countries as well. The filings are based on clinical data from an international phase III randomized trial of 708 GIST patients who had complete surgical resection of their disease and then immediately began treatment with either imatinib 400 mg daily or placebo daily for one year. The primary endpoint was recurrence-free survival (RFS). Results: 98% of patients receiving imatinib remained recurrence-free at one year following surgery compared to 82% of those receiving placebo. This represents an unprecedented 89% reduction in risk of KIT-positive recurrence after surgery in patients treated with imatinib compared to placebo. A decision for final approval is expected within 6 months.

Food for thought: With the adjuvant imatinib for GIST era about to begin, the question of treatment duration will become a hot topic. This trial addressed one year of therapy with trials of 2 years and 3 years ongoing now, but optimal duration is currently unclear.