Feasibility and Safety of Neoadjuvant Alectinib in Pulmonary Invasive Mucinous Adenocarcinoma with ALK Rearrangement: Case Report and Literature Review.

BACKGROUND: Pulmonary invasive mucinous adenocarcinoma (IMA) is a rare variant of lung adenocarcinoma that rarely shows anaplastic lymphoma kinase (ALK) rearrangement. Alectinib (tyrosine kinase inhibitors) has been listed as category 1 recommendations for advanced ALK + NSCLC first-line therapy due to low toxicity and excellent efficacy, and its median progression-free survival is 34.8 months. Here, we report a case of a patient with ALK-rearranged lung IMA who showed favorable results to neoadjuvant alectinib. CASE: A 67-year-old man with no history of smoking was diagnosed with clinical stage as IIIB invasive mucinous adenocarcinoma based on clinical symptoms, chest CT and pathological findings. The anaplastic lymphoma kinase (ALK) fusion status was assessed by real-time PCR. After acquiring informed consent from the patient, we offered neoadjuvant alectinib at a dosage of 150 mg twice per day for three cycles (84 days), all lesions were undetectable on chest CT. Later, a thoracoscopic left lobectomy was performed. The postoperative pathological showed that a small amount of tumor cells remained, and the TNM stage was downstaged as T1aN0M0 IA. CONCLUSION: To our knowledge, this is the first case discussing the treatment of ALK-rearranged IMA of the lung with neoadjuvant alectinib. Alectinib is an effective ALK inhibitor, and in cases of lung adenocarcinoma with ALK rearrangement, alectinib treatment is a reasonable and priority option. Neoadjuvant alectinib may be clinically feasible and well tolerated in locally advanced NSCLC.

Phase II, Open-label, Single-arm, Multicenter Study to Assess the Activity and Safety of Alectinib as Neoadjuvant Treatment in Surgically Resectable Stage III ALK-positive NSCLC: ALNEO Trial.

BACKGROUND: Alectinib is a potent anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) which is currently used in the first-line setting of advanced ALK+ non-small cell lung cancer (NSCLC). Despite favorable results in the metastatic setting, the activity of alectinib in locally-advanced ALK+ NSCLC as a neoadjuvant treatment remains to be assessed. We report the case of a patient with stage IIIA ALK+ NSCLC (cT2aN2) who received alectinib as neoadjuvant treatment, achieving major pathological response (MPR) at pathologic examination. Hence we present the treatment rationale and study design of a phase II, open-label, single-arm, multicenter clinical trial (ALNEO study, EUDRACT number 2020-003432-25). MATERIALS AND METHODS: Patients with potentially resectable stage III ALK+ NSCLC (any T with N2, T4N0-1) will be registered to receive oral alectinib 600 mg twice daily for 2 cycles of 4 weeks each (8 weeks totally) during the neoadjuvant phase. After definitive surgery, patients will enter in the adjuvant setting, during which they will receive alectinib 600 mg twice daily for 24 cycles (96 weeks). The primary endpoint is MPR, defined as ≤10% residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery. Secondary endpoints include pathological complete response, objective response, event-free survival, disease-free survival, overall survival, adverse events. CONCLUSIONS: Our case report supports the feasibility of alectinib as neoadjuvant treatment. ALNEO study will further explore the activity and safety of this novel treatment strategy.