OSI Pharmaceuticals Inc said its phase III Saturn study of Tarceva (erlotinib) as a single agent, first-line maintenance therapy for patients with advanced non-small cell lung cancer (NSCLC), who did not progress first-line treatment with platinum-based chemotherapy, has met both of its co-primary endpoints.

The study met both of its co-primary endpoints by demonstrating a statistically significant 41 per cent improvement in the time patients live without their disease worsening (as measured by progression free survival, or PFS) compared with placebo (Hazard Ratio = 0.71, p-value <0.00001; a hazard ratio of less than one indicates a decreased risk of disease progression and a p-value of less than 0.03 indicates statistical significance) and a 45 per cent increase in the time patients live without their disease worsening compared with placebo in the sub-set of patients who were determined to have tumours expressing the EGFR gene by Immunohistochemistry (IHC) (Hazard Ratio for PFS = 0.69, p-value <0.0001). The study confirmed findings from prior studies in later stage NSCLC patients that Tarceva demonstrated benefit across a broad spectrum of NSCLC patients. Importantly, the study demonstrated a PFS benefit for Tarceva maintenance therapy in both squamous cell carcinoma patients (HR=0.76, p-value=0.0148, n=359); and non-squamous patients (HR=0.68, p-value < 0.0001, n=525).

"The results of the Saturn study offer a clinically meaningful benefit for patients with advanced lung cancer," said professor Federico Cappuzzo, principal investigator on the Saturn study from the Istituto Clinico Humanitas IRCCS, Milan, Italy. "If we can offer patients a once-daily, oral therapy with a favourable safety profile right after chemotherapy to extend the time they live without their disease progressing, this is an important step forward in the treatment of lung cancer."

Pre-planned biomarker analyses of tissue samples collected as part of the Saturn protocol provided important information on the potential role of EGFR mutations and K-ras mutations in predicting possible outcomes of Tarceva therapy in NSCLC patients. The subgroup analysis of patients whose tumours possessed an activating EGFR mutation and were eligible for analysis (n=49) demonstrated a statistically significant ten-fold increase in the time patients live without their disease worsening (as measured by PFS) for patients treated with Tarceva compared with placebo. The hazard ratio was 0.10 (p-value <0.0001). In the sub-population of patients tested for their EGFR mutation or wild-type status, a statistically significant PFS benefit of Tarceva therapy was also evident in patients with wild-type EGFR status after excluding those patients whose tumours had an activating EGFR mutation (HR=0.78, p-value < 0.0185, n=388).

In addition, the sub-group analysis of patients whose tumours possessed a K-ras mutation and were eligible for analysis (n=90) suggested a similar treatment benefit in terms of PFS to that seen in the overall population (HR=0.77, p-value=0.679).

The EGFR IHC status of the tumour was not predictive of outcome for Tarceva therapy in the study as demonstrated by HR of 0.69 in EGFR IHC positive (n=618) and HR of 0.77 in EGFR IHC negative (n=121) patients.

"The biomarker analyses in the Saturn study have shed an important light on the appropriate use of EGFR and K-ras mutation status biomarkers in Tarceva therapy. The data suggest that, while NSCLC patients with wild-type EGFR clearly benefit from Tarceva therapy, those whose tumours contain an EGFR mutation derive pronounced benefit and that those patients whose tumours contain a K-ras mutation should not be excluded from treatment with Tarceva," stated Colin Goddard, chief executive officer of OSI Pharmaceuticals. "Presuming successful regulatory approval, we believe Tarceva will be the therapy of choice for NSCLC patients in the maintenance setting whose tumours possess an EGFR mutation, are of squamous cell histology, or are chemo ineligible while continuing to offer a non-chemotherapy choice for all NSCLC patients in this setting."

Twenty-five per cent of patients treated with Tarceva had not seen their disease progress after six months compared with 15 per cent of patients treated with placebo. Measurements of median PFS in the overall population in the study were impacted by an unusual step-wise data distribution in the Kaplan-Meier analysis (12.3 weeks for the Tarceva arm versus 11.1 weeks for the placebo arm) which is not representative of the robust overall PFS benefit as evident by the Hazard Ratio of 0.71 and an associated p-value of <0.00001.

Overall survival data (a secondary end-point in the study) is immature and is not expected to be available until later in the year. There were no new safety signals seen in the study and using Tarceva maintenance therapy immediately following first-line chemotherapy did not appear to exacerbate any residual chemotherapy related side-effects. Fifty-five percent of patients in the Tarceva arm and 64 per cent of patients on placebo received subsequent therapy after progressing.

Saturn is an international, placebo-controlled, randomized, double-blind, Phase III study conducted by Roche that enrolled 889patients with advanced NSCLC at approximately 160 sites worldwide.

Tarceva is a once-a-day pill that targets the EGFR pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cell, one of the critical growth factors in NSCLC and pancreatic cancers.

OSI Pharma is committed to 'shaping medicine and changing lives' by discovering, developing and commercializing high-quality, novel and differentiated targeted medicines designed to extend life and improve the quality of life for patients with cancer and diabetes/obesity.