Updated median PFS and analysis of quality of life (QOL) in optimal, a phase III, randomized, open-label, first line study of erlotinib vs carboplatin/gemcitabine in patients with advanced nonsmall cell lung cancer (NSCLC) with EGFR activating mutations

Background: OPTIMAL demonstrated superiority of erlotinib (E) vs carboplatin/gemcitabine (G/C) in terms of progression free survival (PFS), objective response rate (ORR) and tolerability in 1st line advanced NSCLC patients with EGFR activating mutations. We update PFS data and firstly report the pre-planned analyses of patients' quality of life (QoL). Methods: Chemonaïve pts with EGFR Act Mut+ advanced NSCLC, ECOG PS 0-2 and measurable disease were randomized to E (150mg/d, until unacceptable toxicity or progressive disease), or G/C (G [1000mg/m2, d1, 8] + C [AUC 5, d1], q 3 wks for up to 4 cycles), and stratified by histology, smoking status and mutation type (n=165). Primary endpoint was PFS. Secondary endpoints including ORR, OS, QoL (FACT-L, TOL, LCS) and safety. Median PFS is updated, the QoL questionnaire was administered at randomization and once every 6 weeks until PD. Clinically relevant improvement during the study was predefined as patient with clinically relevant improvement one or more times during the study. Results: 165 were randomized and 154 included in the study population (82 E; 72 G/C). In the primary analysis, PFS was significantly prolonged with E vs G/C: mPFS of 13.1 vs 4.6, HR 0.16; p<0.0001 (data reported in ESMO 2010). By the cut-off date of Jan 7, 2011, an updated analysis showed median PFS of 13.7 vs 4.6 months, respectively, HR 0.164, p <0.0001). 128 patients with a baseline and at least one post-baseline QoL assessment were included for QoL analysis (74 E; 54 G/C).Compared with G/C group, E had a clinically relevant improvement in QoL, as assessed by scores on the FACT-L ( 73% vs 29.6 %; OR 6.9; 95% CI 3.07-15.48; p<0.0001) and by scores on LCS (75.7% vs 31.5%; OR 6.77; 95% CI 3.04- 15.05; p<0.0001), and by scored on the TOI ( 71.6% vs 24.1%, OR 7.79; 95% CI 3.44-17.66; p<0.0001). Conclusion: Erlotinib demonstrated improved PFS and QoL over G/C, with a more favorable tolerability profile.