Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients: a literature review of 100 cases

Abstract

The discovery of EGFR mutations and EML4-ALK gene rearrangements has radically changed the therapeutic scenario for patients with advanced non-small cell lung cancer. ALK and EGFR tyrosine-kinase inhibitors showed better activity and efficacy than standard chemotherapy in the first and second line treatment settings, leading to a clear advantage in overall survival of advanced non-small cell lung cancer patients harboring these genetic alterations.Historically the coexistence of EGFR mutations and EML4-ALK rearrangements in the same tumor has been described as virtually impossible. Nevertheless many recent observations seem to show that it is not true in all cases.In this review we will discuss the available literature data regarding this rare group of patients in order to give some suggestions useful for their clinical management. Furthermore we report here two cases of concomitant presence of both alterations that will help us in the development of discussion.

Concomitant expression of exon 19 mutation epidermal growth factor receptor and anaplastic lymphoma kinase gene rearrangement in metastatic adenocarcinoma lung responsive to crizotinib

“…[ 5 6 10 ] Patients housing both mutations have shown an objective response and increased sensitivity to ALK-TKI alone[ 11 12 ] but can also be sensitive to both targeted therapies, thus suggesting a variable dependence on EGFR and ALK oncogenes. [ 13 ] Patients with double mutations have a higher incidence of brain metastases[ 14 ] and also renal dissemination as seen in our case, indicating their aggressive nature.…”

“…Rearrangement of ALK with echinoderm microtubule-associated protein-like-4 oncogene on the chromosome-2 short arm in approximately 3%–7% NSCLC adenocarcinoma cases specific for ALK-TKIs such as crizotinib and ceritinib. [ 14 ] EGFR mutations have been known to predominate in well-differentiated while ALK in poorly differentiated adenocarcinomas[ 15 16 ] in young Asian nonsmokers. [ 4 ] However, around 100 cases of concomitant presence have been reported in the world[ 14 ] and only one case in India.…”

“…[ 14 ] EGFR mutations have been known to predominate in well-differentiated while ALK in poorly differentiated adenocarcinomas[ 15 16 ] in young Asian nonsmokers. [ 4 ] However, around 100 cases of concomitant presence have been reported in the world[ 14 ] and only one case in India. [ 4 ] Regarding such coexistence, few have described it to be about 1%,[ 2 ]1.3%,[ 17 ]1.6%,[ 1 ] and even 0.3%.…”

“…With around 100 such concomitant cases reported in the world,[ 14 ] Kamath et al . [ 4 ] have reported the only case in India, while we report the second case in an upfront metastatic patient.…”

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

“…www.nature.com/scientificreports www.nature.com/scientificreports/ with such co-mutations is of clinical importance since these concurrent mutations represent a distinct subset of patients and may have significant impact on treatment outcomes. In this regard, previous studies showed that patients carrying EGFR/ALK co-mutations varied in their sensitivity to and that the choice between these two classes of TKI drugs as first-line treatment for these patients is still being debated 49 . Hence, further studies are required to investigate clinical activity and drug sensitivity of different co-mutation subsets in order to develop suitable treatment approaches.…”