Twelve RCTs (n=7,724) were included. Seven were fully published (n=6,037) and 5 were in abstract form (n=1,687).
Of 9 RCTs evaluating gefitinib, 5 were fully published articles, all of which were double-blinded. Four of the 5 published articles conducted intention-to-treat analyses and/or followed up 99% of the participants. The phase III studies (4 of the 5 published articles) utilised data-monitoring committees. Limited data were available on the quality of the 4 RCTs of gefitinib reported as abstracts or slide presentations. Of the 3 RCTs of erlotinib (all phase III), 2 of which were fully published, at least 1 was double-blinded and analysed by intention-to-treat. Nine of the 12 studies reported associations with pharmaceutical companies.
First-line treatment (2 RCTs, n=2,130).
Among patients on platinum-based chemotherapy receiving concurrent gefitinib (250 or 500 mg) or placebo, there were no statistically significant differences at 12 months between the groups for symptom control, survival, tumour response or median time to progression. Adverse events were similar in all study arms, with the exception of dose-related diarrhoea and skin disorders associated with gefitinib. Withdrawal from treatment due to adverse events (2 RCTs) and infections (1 RCT) were also significantly more common in the gefitinib arms, especially the 500-mg arm. Maintenance therapy (1 RCT, n=255).
Among patients with unresected NSCLC without disease progression after chemoradiation and consolidation therapy, who were receiving gefitinib (250 mg) or placebo as maintenance therapy, there was no statistically significant difference in survival rates between the groups.
Second-line or later treatment (2 RCTs).
In one RCT (n=1,692) gefitinib provided no statistically significant overall survival benefit over BSC for patients who failed to respond or could not tolerate chemotherapy, though symptom scores were significantly more improved in the intervention group (p=0.019). Subgroup analysis showed a statistically significant benefit in survival times among patients who had never smoked (HR 0.67, 95% CI: 0.49, 0.92) and among patients of Asian origin (HR 0.66, 95% CI: 0.48, 0.91). A second RCT, comparing docetaxel with gefitinib (250 mg), reported similar tumour response, median survival rates and QOL outcomes in the two groups.
Dose comparisons (2 RCTs, n=425).
Among patients with relapsed or recurrent NSCLC, tumour response and survival rates were similar among patients on 250 or 500 mg gefitinib. The median time to symptom improvement in symptomatic patients was 8 days (1 RCT). Toxicity was generally higher in the 500-mg group.
The review also referred to preliminary data from 2 RCTs of gefitinib used as first- or second-line therapy in combination with chemotherapy.
First-line treatment (2 RCTs, n=2,231).
Among patients on platinum-based chemotherapy receiving concurrent and maintenance erlotinib (150 mg) or placebo, there were no statistically significant differences overall between the groups in survival, time to disease or symptom progression rates. In subgroup analysis, never-smokers in 1 RCT had significantly increased median survival time (22.5 months versus 10.1 months, p=0.001) and time to disease progression (6 months versus 4.3 months, p=0.002). Among patients receiving erlotinib those with EGFR mutations had a significantly higher tumour response rate than those without (53% versus 18%, p<0.01), though there was no statistically significant difference in survival rates. The difference in tumour response rate did not apply in the placebo group. One of the RCTs reported a higher incidence of serious adverse events in the erlotinib arm.
Second-line or later treatment (1 RCT, n=731).
Among patients with relapsed or recurrent NSCLC taking erlotinib or placebo, a statistically and clinically significant benefit was reported in median overall survival (6.7 months versus 4.7 months; HR 0.61, p=<0.001) and progression-free survival (2.2 months versus 1.8 months; HR 0.61, p=<0.001) in the erlotinib group. In this group, tumour response rates were higher among women, nonsmokers, Asians and patients with adenocarcinoma (p=<0.02). QOL measures showed a statistically significant benefit of erlotinib in several patient-reported symptoms including cough, dyspnoea and pain (adjusted p=<0.04). Toxicity was similar between the groups, though rash and diarrhoea occurred more frequently in the erlotinib arm.