A Narrative Review of the Cases of Co-altered EGFR and ALK in Non-small Cell Lung Cancers: An Attempt to Break the Therapeutic Dilemma

Molecular profiling is essential in advanced non-small cell lung cancer (NSCLC) to identify actionable genetic alterations and guide targeted therapies.While epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are historically considered mutually exclusive alterations, numerous cases of co-occurring EGFR and ALK alterations (CA-EGFR/ALK) have been reported.Currently, the clinicopathological profile of this co-altered patient population remains poorly understood, and no established clinical consensus exists regarding optimal treatment sequencing.Our objective was to evaluate the published data related to CA-EGFR/ALK in terms of clinicopathologic features, the pattern of therapy, response to therapy, and survival.This was a retrospective analysis of published literature related to the subject.Relevant case reports, institutional data analyses, review articles, and editorials were searched, and all relevant case reports and research papers with CA-EGFR/ALK were included without any exclusion criteria.The pooled data of a total of 300 cases showed an Asian and female preponderance with a median age of 57.Smoking history was noted in 22.7%, and adenocarcinoma was the most common histology, with predominant acinar and solid patterns.The most prevalent EGFR mutations were Del 19 and L858R.While response rates to anti-EGFR and ALK therapies have generally been favorable, there are varied results and interpretations.There were no statistical differences in disease control rates (DCR) among EGFR, ALK, or a combination of therapies.Most studies have utilized first-generation anti-EGFR drugs and crizotinib.Moreover, the reported survival outcomes exhibit inconsistencies across the published literature.The key takeaway messages from 41 studies are presented in the table for greater insight.The largest collective interpretation of the data to date is anticipated to provide deeper insight into the natural history and clinicopathological profile of these cases and help select precision therapies.There exists a clear need for research to identify the preferred anti-EGFR or ALK drugs and the role of combination therapies.