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1. Patients with previously platinum-sensitive ovarian cancer showed no increase in progression-free survival or overall survival when randomized to two years Erlotinib treatment as compared to observation.
2. Post-hoc stratification of patient subgroups by age, stage, type of first-line chemotherapy, and response type to chemotherapy failed to show any group-specific advantage in either study groups.
Evidence rating Level: 1 (Excellent)
Study Rundown: This study, led by the European Organisation for Research and Treatment of Cancer- Gynaecological Cancer Group, is the first to inspect the effectiveness of a receptor tyrosine kinase inhibitor as maintenance therapy in patients who have had progression-free survival (PFS) after initial platinum-based chemotherapy. They showed that there was no difference in PFS nor overall survival (OS) for patients randomized to either Erlotinib (Tarceva) or observation. While the treatment period was designed to be two years, the median duration of Erlotinib treatment was 244 days and 107 patients (25.8%) stopped treatment due to severe adverse effects, primarily diarrhea or rash. Interestingly, while positive flourescent in-situ hybridization EGFR status had worst OS as compared to negative EGFR status (46.1 vs 67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P=0.044) overall, there was no correlation between EGFR status and PFS, OS, and withdrawal from treatment due to adverse effects within the Erlotinib treatment arm itself. Erlotinib has been shown to have only modest success in treating non-small cell lung cancer. This study also reiterates the difficulty of finding a prognostic biomarker, as EGFR mutational status did not correlate to treatment response. Another limitation of this trial was that it was not placebo controlled, a decision that was not addressed by the authors.
In-Depth [randomized-controlled study]: This study was a phase III randomized controlled trial that included 835 patients from 125 institutions in 10 countries. Patients with stage II-IV ovarian epithelial cancers who previously responded to platinum-based chemotherapy were randomized to either two year treatment with the receptor tyrosine kinase inhibitor, Erlotinib (n=420), or observation (n=415). The primary endpoint was PFS and secondary endpoints were OS, toxicity, incidence of rash, and quality of life. The median progression free survival (PFS) in the Erlotinib arm as compared to the observation arm were 12.7 and 12.4 months, respectively (stratification-adjusted HR, 1.05; 95% CI, 0.90 to 1.23; P=0.525) while the overall survial (OS) were 50.8 and 59.1 months, respectively (HR, 0.99; 95% CI, 0.81 to 1.20; P=0.903). Patients were stratified by FIGO stage, institution, age (>65 versus <65 years old), type of first-line therapy, and clinical response to first-line therapy. The analysis was performed according to intention-to-treat and the median follow-up time was 51 months. Survival was approximated using the Kaplan-Meier method and the durability of treatment response was analyzed using forest plots with heterogeneity tests. Quality of life measures were limited by low compliance (<50% by the second year).
By Khang T. Dinh
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