Efficacy of dacomitinib in patients with non-small cell lung cancer carrying complex mutations: a real-world study.

Background: Dacomitinib is a first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor () mutations; however, clinical evidence of its activity on NSCLC with complex mutations is limited.

Methods: Patients harboring complex (common mutations co-existing with uncommon mutations), or common (comparison cohort) mutations, who were treated with dacomitinib, were retrospectively evaluated in the Chinese National Cancer Center and the China PLA hospital between August 2019 and August 2021.

Results: In total, 72 patients with NSCLC harboring complex (C+U group, n=18) or common (C group, n=54) mutations and being treated with dacomitinib were enrolled. In the C+U group, 16 cases (88.9%) harbored L858R mutations co-existing with uncommon mutations located from exon 18 to exon 25 of (mostly E709X), and two cases harbored exon 19 deletion co-existing with G724S or K754E. Among the 15 evaluable patients, the objective response rate (ORR) was 40% (6/15), and the disease control rate (DCR) was 73.3% (11/15). The median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI), 4.4-10.6 months]. Except for the application line of dacomitinib (P=0.039), no significant statistical differences were found in other characteristics and adverse events between the two groups. The Kaplan-Meier method revealed no significant differences in PFS (P=0.889) and overall survival (OS) (P=0.703). However, the stratified analysis found worse PFS in the C+U group than that observed in the C group when receiving 1 and ≥3 line dacomitinib treatment, while its OS was worse than that of group C when receiving ≥3 line treatment. Furthermore, in a multivariate analysis, complex mutation status was an independent prognostic factor for OS (P0.038) in the entire cohort.

Conclusions: This study indicated a worse response and prognosis of patients with NSCLC harboring complex mutations than those harboring common mutations when treated with dacomitinib. Further studies and data are needed to confirm this conclusion.