ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

Abstract

BackgroundAlthough anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown.Case presentationWe discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size.ConclusionsTo the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.

ALK-Positive Squamous Cell Carcinoma Dramatically Responded to Alectinib

“…Tamiya et al reported a case wherein the patient had a heavy smoking history and did not respond well to alectinib [ 3 ]. However, Mamesaya et al reported an ALK-positive patient with SCC without smoking history who was successfully treated with alectinib [ 4 ], which was similar to our case. These cases implied that smoking status may be a predicting factor for alectinib treatment in ALK-positive patients with SCC.…”

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

“…Thus, EGFR and its ligands may have critical roles in ALK-rearranged Sq-LC as an off-target mechanism of alectinib resistance. On the other hand, a case of successful management of ALK-rearranged Sq-LC by initial treatment with alectinib has been reported [ 19 ], although additional cases must be studied in order to determine whether this is a general phenomenon.…”

Next-Generation Sequencing at High Sequencing Depth as a Tool to Study the Evolution of Metastasis Driven by Genetic Change Events of Lung Squamous Cell Carcinoma

“…The variants CDKN2A (p.Leu65Pro) and ALK (p.Ile1461Val) were found in another patient also with lung SqCC, with the same variant frequency (data not shown). Somatic alterations of ALK gene are reported relatively rarely in squamous cell carcinoma (SqCC) (48), but, on the other hand, CDKN2A alterations are common and have been reported in FIGURE 4 | Pathogenicity web plotting prediction scores for the three variants, FGFR3 (p.Ser249Cys) (left side), CDKN2A (p.Leu16Profs *9) (middle side), and HRAS (p.Gh161Pro) (right side). Values are scaled so that the most pathogenic scores are plotted toward the external circles.…”

“…The variants CDKN2A (p.Leu65Pro) and ALK (p.Ile1461Val) were found in another patient also with lung SqCC, with the same variant frequency (data not shown). Somatic alterations of ALK gene are reported relatively rarely in squamous cell carcinoma (SqCC) ( 48 ), but, on the other hand, CDKN2A alterations are common and have been reported in recent genomic studies of lung SqCC ( 49 ). Interestingly, in one recent study, which included three patients with lung SqCC, the rate of concordance in somatic mutations between local metastasis in distinct lung lymph nodes and primary lung cancer varies from 15 to 82%, and some nodes have highly similar somatic mutation profiles ( 45 ).…”