Background: Patients harboring concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) arrangements constitute a small subgroup of non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR tyrosine kinase inhibitors (TKIs) and the ALK-specific TKI crizotinib in these patients has not been well-established.
Objective: This study investigated the efficacy of targeted therapies in these patients compared with patients with EGFR or ALK alterations alone.
Methods: Patients were screened for EGFR mutation and ALK rearrangement at the Shanghai Chest Hospital (2011-2017). Progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) were retrospectively analyzed.
Results: A total of 5816 patients were screened, and 26 patients were identified as having concomitant EGFR mutations and ALK rearrangements; 22 patients were eligible for survival analysis. Additionally, 95 EGFR-mutant patients and 60 ALK-rearranged patients were randomly selected for analysis. The ORR to EGFR TKIs was 63.2% (12/19) for EGFR/ALK co-altered patients and 62.1% (59/95) for EGFR-mutant patients (p = 0.93) with a median PFS of 10.3 and 11.4 months, respectively (hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.59-1.57; p = 0.87). The ORR to crizotinib was 66.7% (8/12) for double-positive patients and 65.0% (39/60) for ALK-rearranged patients (p = 1.00), with a median PFS of 11.1 and 12.5 months, respectively (HR 1.39; 95% CI 0.69-2.80; p = 0.28). OS was 27.1, 36.2, and 36.8 months for EGFR-mutant, ALK-rearranged, and EGFR/ALK co-altered patients, respectively, and the EGFR/ALK co-existing subgroup tended to have a longer survival period than EGFR-mutant cohorts, though no statistical difference was found (p = 0.12). The median PFS of crizotinib as a sequential therapy after failure of EGFR TKIs was 15.0 months, which exhibited no statistically significant difference compared with the median PFS of ALK-altered patients who received crizotinib (p = 0.80).
Conclusions: Both first-generation EGFR TKIs and the ALK TKI crizotinib were effective in these patients. Sequential treatment with EGFR TKIs and crizotinib should be considered as a management option.