Coexistence of EGFR mutation and ALK translocation in NSCLC: Literature review and case report of response to gefitinib

Santelmo, Carlotta; Ravaioli, Alberto; Barzotti, Eleonora; Papi, Maximilian; Poggi, B.; Drudi, Fabrizio; Mangianti, M.; Salvi, Mario; Crinò, Lucio

doi:10.1016/j.lungcan.2013.04.009

Cited by 33 publications

(20 citation statements)

References 26 publications

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“…Our result is not consistent with other studies of the characteristics of adenocarcinoma and EGFR mutation type (Tiseo et al, 2011;Santelmo et al, 2013), which suggested that the association between EGFR and female never-smokers might be limited to EGFR mutations in exon 21.…”

Section: Discussioncontrasting

confidence: 99%

“…Several case reports indicated that the presence of concomitant EGFR mutations and ALK rearrangements might be associated with mutual resistance to single-agent crizotinib or EGFR-TKIs (Shaw et al, 2009;Sasaki et al, 2011;Tiseo et al, 2011;Tanaka et al, 2012). Other studies reported good response to EGFR-TKIs (Wang et al, 2012;Santelmo et al, 2013;Yang et al, 2014) or crizotinib Yang et al, 2014). According to a previous study, the objective response rate (80%) for first-line EGFR-TKIs in EGFR/ALK co-altered tumors was similar to that in patients with pure EGFR mutations .…”

Section: Discussionmentioning

confidence: 92%

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Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Lei

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangements and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been intensively studied. The objective of this study was to determine the clinicopathological characteristics in genotype-specific subsets of patients with NSCLC to help ensure the optimal identification of patients whose tumors harbor these two driver mutations. The incidence of ALK rearrangements was investigated in 763 NSCLC specimens by immunohistochemistry using a D5F3 antibody, and EGFR mutations were assessed by amplification refractory mutation system (ARMS) in 222 patients with lung adenocarcinoma. Of these, 73 (9.6%) were detected as being ALK-positive; this designation was associated with young age, female gender, never-smokers, lymph node metastasis, and poor tumor differentiation, but not with histology. EGFR mutations were identified in 102 (45.9%) of 222 adenocarcinoma samples, and were more frequent in females and never-smokers. No difference in age was observed. Specifically, we identified several cases of complex EGFR mutations, and concomitant EGFR mutations and ALK rearrangements. These results suggest that young women and never-smokers are at risk for ALK rearrangement. We also identified concomitant mutations of EGFR and rearrangements of ALK in this study.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 92%

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Lei

Wang

et al. 2015

Genet. Mol. Res.

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“…A clinical response to EGFR-TKIs in patients with EML4-ALK -positive lung adenocarcinoma has been previously observed in cases that harbour a coexisting EGFR mutation and EML4-ALK translocation (13–15). However, discordant results have been reported by studies investigating tumours with these concomitant molecular alterations, resulting in resistance and response to the same drug being reported by different studies (13–17).…”

Section: Discussionmentioning

confidence: 80%

Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report

et al. 2015

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Lung cancer is the leading cause of cancer-associated mortality worldwide, and the mainstay of treatment remains to be personalised therapy. Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have been reported to exert a significant impact in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harbouring mutations in the EGFR gene. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation has been described in a subset of patients with NSCLC and possesses potent oncogenic activity. This translocation represents one of the most novel molecular targets in the treatment of NSCLC. Patients who harbour the EML4-ALK rearrangement possess lung tumours that lack EGFR or K-ras mutations. The present study reports the case of a patient possessing the EML4-ALK rearrangement that was initially treated with erlotinib and achieved a lasting clinical response. To the best of our knowledge, the current study is the first report of a clinical response to EGFR-TKI in a patient with lung adenocarcinoma harbouring the EML4-ALK fusion gene, but no EGFR mutations. However, as the disease progressed, the ALK gene status of the tumour was investigated, and based upon a positive result, the patient was treated with crizotinib and achieved a complete response. In conclusion, the present study suggests that the EML4-ALK rearrangement is not always associated with resistance to EGFR-TKIs. Further studies are required to clarify the biological features of these tumours and to investigate the mechanisms underlying the primary resistance to EGFR-TKIs when the EML4-ALK rearrangement is present.

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“…One of these patients received TKIs and crizotinib during the treatment period, and both regimens showed a disease control response. Although EGFR mutations and ALK translocations are generally considered mutually exclusive, sporadic cases with concomitant EGFR and ALK alteration have been reported . The prevalence of dual positive cases differed and their responses to EGFR and/or ALK inhibitors were conflicting.…”

Section: Discussionmentioning

confidence: 99%

Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

Hao

Wang

et al. 2016

Thoracic Cancer

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BackgroundThe efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations.MethodsThe clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS).ResultsThe gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2.ConclusionsPemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC.

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Coexistence of EGFR mutation and ALK translocation in NSCLC: Literature review and case report of response to gefitinib

Cited by 33 publications

References 26 publications

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report

Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

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