Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer

BACKGROUNDErlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date. METHODSPatients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan. RESULTSIn total, 92 eligible patients were studied, including 42 with and 50 without an EGFR-sensitizing mutation. The EGFR-mutant cohort had a slower rate of progression (P=.003) and a longer TTC (P<.001). Among the patients with EGFR-mutant cancers, 28 (66%) continued single-agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC. CONCLUSIONSA change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases. Cancer 2015;121:2570-2577. (c) 2015 American Cancer Society. Anecdotal experience suggests that some patients with non-small cell lung cancer who progress on erlotinib can have continued disease control without a change in treatment. In this analysis, investigators study 92 patients with non-small cell lung cancer who develop objective disease progression while receiving first-line erlotinib on 3 clinical trials and demonstrate the potential benefits of delaying a change in treatment for patients who have epidermal growth factor receptor-mutant lung cancer and favorable progression characteristics.