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Clinical Management of Non-Small Cell Lung Cancer with Concomitant EGFR Mutations and ALK Rearrangements: Efficacy of EGFR Tyrosine Kinase Inhibitors and Crizotinib

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Abstract

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.

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Acknowledgements

The authors acknowledge all the patients and their families for their contributions to this study. No writing assistance was received.

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Author notes

  1. Yiming Zhao and Shuyuan Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Huaihai west road NO. 241, Shanghai, 230032, China

    Yiming Zhao, Shuyuan Wang, Bo Zhang, Rong Qiao, Jianlin Xu, Lele Zhang, Yanwei Zhang & Baohui Han

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Correspondence to Baohui Han.

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Yiming Zhao, Shuyuan Wang, Bo Zhang, Rong Qiao, Jianlin Xu, Lele Zhang, Yanwei Zhang and Baohui Han have no conflicts of interest that might be relevant to the contents of this manuscript.

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Zhao, Y., Wang, S., Zhang, B. et al. Clinical Management of Non-Small Cell Lung Cancer with Concomitant EGFR Mutations and ALK Rearrangements: Efficacy of EGFR Tyrosine Kinase Inhibitors and Crizotinib. Targ Oncol 14, 169–178 (2019). https://doi.org/10.1007/s11523-019-00628-6

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