EGFR mutations, ALK translocations not mutually exclusive in NSCLC

By Shreeya Nanda, Senior medwireNews Reporter

Researchers from the Republic of Korea have found that epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations can occur concomitantly in a proportion of patients with non-small-cell lung cancer (NSCLC).

The frequency of concomitant detection increases with increasing sensitivity of detection methods for EGFR mutations, observe Yoon Kyung Jeon (Seoul National University Hospital) and colleagues in the Annals of Oncology.

The researchers explain that EGFR mutations and ALK translocations are considered to be mutually exclusive in NSCLC, but given the incidence of sporadic so-called dual positive cases, they sought to assess the prevalence of alterations in both genes.

The study included 1455 patients with NSCLC who had been screened for EGFR mutations by direct Sanger sequencing and ALK translocation by fluorescence in situ hybridisation. Samples from the 91 patients with ALK translocations were further analysed for EGFR mutations by increasingly sensitive methods: peptide nucleic acid (PNA)-clamping real-time polymerase chain reaction (PCR), targeted next-generation sequencing (NGS) and mutant-enriched NGS.

Direct EGFR sequencing identified four cases with concomitant EGFR and ALK alterations, equating to 4.4% of NSCLC patients with ALK translocations and 0.7% of those with EGFR mutations.

When PNA-clamping real-time PCR was used, the number of dual positive cases increased to 8.8% of ALK-translocated NSCLCs, with a further increase to 12.1% and 15.4% with targeted NGS and mutant-enriched NGS, respectively.

Jeon et al also evaluated the responsiveness to treatment with an EGFR–tyrosine kinase inhibitor (TKI) and/or an ALK inhibitor in the dual positive patients. Of the three patients who received the EGFR–TKI gefitinib, one had stable disease while two progressed.

By contrast, the response to the ALK inhibitors crizotinib or ceritinib was better, with seven of eight patients achieving a partial response and one patient exhibiting stable disease, the team reports.

The researchers caution, however, that the role of EGFR and ALK inhibitors in dual positive patients is “not straightforward” and that further studies on the appropriate management of these patients are warranted.

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