In its clinical guideline on lung cancer, NICE recommends docetaxel monotherapy as an option for the second-line treatment of locally advanced or metastatic NSCLC in patients who have relapsed following previous chemotherapy. Erlotinib is recommended as an alternative to docetaxel in this setting (TA162), provided that it is provided at an overall treatment cost equal to that of docetaxel (it is not however recommended for use in patients for whom docetaxel is unsuitable). Docetaxel has however since come off patent.
The benefit of EGFR TKIs varies widely between patients with EGFR mutations and those with wild-type EGFR. The authors of this research note that there have been a number of studies comparing EGFR tyrosine kinase inhibitors to chemotherapy in the second-line treatment of non-small cell lung cancer (NSCLC); none were however specifically designed to address the role of EGFR genotype as a predictive marker. Although retrospective analyses have been conducted, these have been limited by the fact that sizeable proportions of the study populations had unknown EGFR status.
Although EGFR TKIs are generally more efficacious than chemotherapy for patients with EGFR-mutated tumours, their value in patients with wild-type EGFR remains controversial. The purpose of the current study (TAILOR) was to determine which second-line treatment is preferable in patients with wild-type EGFR – erlotinib or docetaxel. A total of 702 patients with metastatic NSCLC who had received previous platinum-based chemotherapy were registered, 504 were genotyped, and 222 (with wild-type EGFR) were enrolled and randomised to docetaxel (n=110) or erlotinib (n=112).
Docetaxel was associated with 2.8-month improvement in median overall survival versus erlotinib (adjusted hazard ratio 0.73; 95% CI 0.53-1.00; p=0.05), with 1 year survival rates of 39.6% versus 31.8%, respectively. Erlotinib was not shown to be better than docetaxel in any subgroup, including non-smokers and wild-type KRAS carriers (although these analyses would have not been sufficiently powered and are therefore hypothesis-generating only). Neutropenia, neurological toxic effects, alopecia, asthenia and nausea were more common with docetaxel, whereas most patients randomised to erlotinib had skin toxicity. The need for treatment delays or dose adjustments due to toxicity was similar between groups.
The authors conclude that chemotherapy should remain the second-line treatment of choice for patients with NSCLC and wild-type EGFR status. They go on to discuss other trial results, including those showing a similar situation in the first-line setting, and its limitations: for example the proportion with adenocarcinoma was higher than expected (69%), and they were unable to properly assess the predictive role of KRAS mutation status.
The authors of a related Comment article say that this study was well designed and correctly interpreted, and that the results could change practice. They comment on the results in the smoking and adenocarcinoma subgroups (both of which are associated with an increased likelihood of EGFR mutation) and suggest that such clinical and pathological features should not be considered as surrogates for EGFR status when selecting treatment, and that every effort should be made to obtain a tumour sample.