[Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement]

Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly.

A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later.

The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI.

Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI.