EGFR-tyrosine-kinase inhibitors (EGFR TKIs) have become established as a standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) who have activating EGFR mutations, and NICE has recommended erlotinib and gefitinib as options for this patient group (TA192 and TA258).
The Phase III FASTACT-2 trial investigated erlotinib intercalated with chemotherapy in the first-line treatment of East Asian patients with stage III/IV NSCLC. The intercalated approach involves intermittent dosing of an EGFR tyrosine kinase inhibitor (TKI) with chemotherapy to achieve pharmacodynamic separation, based on the rationale that the EGFR TKIs cause G1 cell-cycle arrest, which inhibits the cell-cycle-dependent cytotoxic effects of chemotherapy. It has been suggested that this may explain the negative findings of earlier combination studies, which utilised standard daily dosing of EGFR TKIs.
As this study does not compare the intercalated approach versus an EGFR TKI alone (current standard treatment) in patients with EGFR-mutation-positive tumours, it is not known if combination chemotherapy and EGFR-TKI treatment is a viable first-line option for these patients. In addition the results are for an East Asian population, and therefore cannot be immediately translated to clinical practice in western populations.