According to results from the multicentre Phase III TITAN (Tarceva In Treatment of Advanced NSCLC) study, erlotinib is associated with a similar survival to docetaxel or pemetrexed when used in the second-line treatment of advanced non-small cell lung cancer (NSCLC).
The authors note that first-line treatment for advanced NSCLC is usually a platinum-based chemotherapy doublet. Available options for second-line treatment include further chemotherapy (e.g. gemcitabine plus taxane; docetaxel; pemetrexed) or targeted drugs (e.g. erlotinib). The EGFR tyrosine kinase inhibitor erlotinib has been found to delay disease progression and increase survival in the second-line setting when compared to placebo; the current III study compared it head-to-head with other treatment options (single-agent docetaxel or pemetrexed).
A total of 2,590 patients with locally advanced, recurrent, or metastatic NSCLC entered the run-in phase and were treated first-line with up to four cycles of first-line platinum doublet chemotherapy. A total of 424 of these had progressive disease during or immediately after treatment and were randomised to open-label second-line treatment with erlotinib (150mg daily; n=203) or chemotherapy (standard docetaxel or pemetrexed; n=221). Treatment was continued until the occurrence of unacceptable toxicity, disease progression, or death. Randomisation was stratified according to stage of disease (IIIb versus IV), ECOG performance status (0/1 or 2), smoking history, and region. The primary endpoint was overall survival (OS).
Enrolment into TITAN was halted prematurely due to slow recruitment; the power of the study was therefore reduced to about 60% and as a result some of the analyses were underpowered to detect clinically meaningful treatment effects. TITAN was a post-approval commitment study for both the FDA and EMA, and both were consulted and agreed on the premature discontinuation.
After a median follow-up of 24-28 months, the median OS was 5.3 months (95% CI 4.0-6.0) in the erlotinib group and 5.5 months (4.4-7.1) in the chemotherapy group (hazard ratio [HR] 0.96, 95% CI 0.78-1.19; p=0.73). Of note, there was also no difference in OS between treatments in those patients with EGFR wild-type disease or in those patients with EGFR-activating mutations; the patient numbers in these subgroups were however too small to allow any conclusions to be made. The authors comment that the choice of the two chemotherapy options (pemetrexed or docetaxel) was not randomised and caution should therefore be exercised when making specific comparisons between erlotinib versus each agent alone. The adverse-event profiles of each treatment were as previously reported, with rash and diarrhoea more common with erlotinib, and alopecia more commonly seen with chemotherapy.
The authors conclude that tolerability and patient preferences are likely to play a crucial role when making second-line treatment decisions for patients with advanced NSCLC, in the absence of any notable differences in efficacy between erlotinib and second-line chemotherapy.
[Editor’s note: Erlotinib is approved by NICE as an alternative to docetaxel in the second-line treatment of advanced NSCLC, if it is provided at an overall treatment cost equal to that of docetaxel (TA 162; November 2008)].