CHICAGO—Erlotinib improved progression-free survival (PFS) when compared with gemcitabine + carboplatin (GC) as first-line treatment for EGFR-activating mutation-positive (EGFR Act Mut+) advanced non-small cell lung cancer, according to the results of the OPTIMAL study presented at the American Society of Clinical Oncology’s 2011 Annual Meeting.

Caicun Zhou, MD, from Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, and colleagues, presented updated PFS data and the first report of the preplanned quality of life (QOL) analyses from the OPTIMAL study, which demonstrated the superiority of erlotinib vs. GC in terms of PFS, objective response rate (ORR), and tolerability in first-line advanced NSCLC patients with EGFR Act Mut+ disease.

A total of 165 chemotherapy-naïve patients with EGFR Act Mut+ advanced NSCLC (ECOG PS 0–2 and measurable disease) were randomized to erlotinib 150mg/day (until unacceptable toxicity or progressive disease) or gemcitabine 1000mg/m2 on Days 1 and 8 + carboplatin AUC=5mg/mL/min on Day 1 every 3 weeks for up to four cycles. Subjects were stratified by histology, smoking status, and mutation type. The primary endpoint was PFS, while secondary endpoints included ORR, overall survival, QOL (FACT-L, TOI, LCSS) and safety. The QOL questionnaire was administered at randomization and every 6 weeks until progressive disease. Clinical improvement in QOL was predefined as an improvement of ≥6 total points on the FACT-L and TOI, or an improvement of ≥2 total points on the LCSS. P-values for QOL were calculated with logistic regression, with PS, smoking history and gender as covariates.

Of 165 patients randomized, 154 were included in the study population (82 erlotinib; 72 GC). In the primary analysis, PFS was significantly prolonged with erlotinib vs. GC: median PFS of 13.1 vs. 4.6 months; HR 0.16; P<0.0001. By the cut-off date of January 7, 2011, an updated analysis showed median PFS of 13.7 vs. 4.6 months; HR 0.164; P<0.0001). Patients with a baseline and ≥1 post-baseline QOL assessment (n=128; 83.2% of study patients) were included in the QOL analysis (74 erlotinib; 54 GC). Compared with the GC group, the erlotinib group had a clinically relevant improvement in QOL, as assessed by scores on the FACT-L (73% vs. 29.6%; odds ratio [OR] 6.9 [3.07–15.48]; P<0.0001), the LCSS (75.7% vs. 31.5%; OR 6.77 [3.04–15.05]; P<0.0001) and the TOI (71.6% vs. 24.1%; OR 7.79 [3.44–17.66]; P<0.0001).

Dr. Zhou et al conclude that patients’ QOL was significantly improved with erlotinib vs. gemcitabine + carboplatin therapy. The investigators also found that erlotinib improved PFS compared with GC as first-line treatment for EGFR Act Mut+ NSCLC.