Characteristics and Response to Crizotinib in ALK-Rearranged, Advanced Non-Adenocarcinoma, Non-Small Cell Lung Cancer (NA-NSCLC) Patients: a Retrospective Study and Literature Review

Abstract

Background

Oncogenic fusion genes consisting of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) can be detected in 5–7% of lung adenocarcinoma cases. The prevalence of ALK rearrangement in non-adenocarcinoma, non-small cell lung cancers (NA-NSCLC) is currently unknown. In addition, the efficacy of crizotinib in these patients has not been well established.

Objectives

The aim of this study was to investigate the prevalence of ALK rearrangement in NA-NSCLC patients and the therapeutic efficacy of crizotinib in these patients.

Methods

We included NA-NSCLC patients who were tested for the presence of ALK rearrangement in our institution from January 2013 to May 2018. The effectiveness of crizotinib in ALK-positive patients was retrospectively analyzed. A literature review was performed and eligible previously published cases were analyzed in combination with our data.

Results

A total of 4662 patients were screened and 1696 NA-NSCLC patients were tested for the presence of ALK rearrangement during the study period. Thirty-two positive patients were identified (1.9%, 95% CI, 1.2–2.5%). A statistically higher percentage of younger (58.0 vs. 63.0, p = 0.01), female patients (53.1% vs. 10.8%, p < 0.01) who were non-smokers (71.9% vs. 40.6%, p < 0.01) and whose tumors contained adenocarcinoma components (34.4% vs. 6.1%, p < 0.01) were observed in the ALK-positive group. Eighteen patients were excluded from the study and 14 eligible patients were included for survival analysis. The median duration of crizotinib treatment (MDT) as a proxy for progression-free survival of the 14 eligible patients in our institution was 6.0 months (95% CI, 1.2–10.8 months). We combined our data with sporadic cases from 16 previous publications (total n = 37) and found that the MDT was 7.0 months (95% CI, 6.0–8.0 months).

Conclusions

Our study suggests the opportunity to test ALK rearrangement in NA-NSCLC patients, especially in younger, female, non-smoking patients containing adenocarcinoma components. Crizotinib provides an option for the treatment of NA-NSCLC patients who have an ALK rearrangement.

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