Subsequent lines of treatment options

There is one randomised controlled trial that studied the role of erlotinib after failure of first or second line chemotherapy.43In this international, phase 3 randomised double-blinded, placebo controlled trial, 731 patients who had received 1 or 2 prior lines of chemotherapy were randomly assigned in a 2:1 ratio to receive erlotinib or placebo. The primary endpoint of OS was met (6.7 months vs. 4.7 months HR 0.7 95% CI 0.58 0.85; p < 0.001). There were significantly more overall responses in the erlotinib group (8.9% vs. < 1%; p < 0.001). The median progression free survival was significantly longer in the erlotinib group (2.2 months vs. 1.8 months HR 0.61 95% CI 0.51 0.74; p < 0.001). We are however mindful that patients enrolled on this trial are unselected and therefore extrapolation of this data in the current era of molecular subtyping must be done so with care. Nevertheless, this trial did provide clinically meaningful prolongation of survival despite heavy pretreatment of 50% of the enrolled patients.

Recommendations on Subsequent Lines of Chemotherapy for Advanced NSCLC

1. The workgroup unanimously recommends to first consider clinical trials.

2. Erlotinib can be considered in the treatment of advanced lung cancer beyond second line chemotherapy in patients with unknown EGFR status or EGFR WT who have not received EGFR TKI (Level II, B).

3. Given the burgeoning pipeline of novel therapeutics addressing either distinct genetic drivers or resistance mechanisms, molecular profiling for actionable alterations either from archival tissue, or a repeat biopsy is also a reasonable consideration (workgroup consensus).

All recommendations are unanimous.