Alectinib activity in chemotherapy-refractory metastatic RET-rearranged non-small cell lung carcinomas: A case series

Abstract

Objectives: to report outcomes of four cases of chemo-refractory RET-rearranged non-small cell lung carcinomas (NSCLCs) treated with alectinib in a single center. Materials and methods: we retrospectively assessed and reported the activity and tolerability of alectinib 600 mg twice daily in advanced and chemo-refractory RET-rearranged NSCLC patients treated in a Brazilian institution. Identification of RET rearrangements was performed using the FoundationOne® next-generation sequencing (NGS) platform. Results: The four patients herein reported were white, female and non-smokers, ranging between 59-66 years of age. All patients had been previously treated with chemotherapy and were TKI naïve; three of them presented disease progression to nivolumab as well. Molecular tumor profiling showed a KIF5B-RET fusion in three patients and a CCDC6-RET in the fourth. One patient exhibited disease progression and clinical deterioration two months after treatment initiation. Disease control was documented in two patients with PFS ranging from 4 to 5 months (one partial metabolic response and one stable disease). In one of the cases, which developed oligoprogression on alectinib, radiation therapy plus post-progression alectinib were able to provide additional disease control for 9 more months. No grade 3/4 adverse events, dose reductions or discontinuation due to toxicity were documented. Conclusion: Although this is a small single center evaluation, alectinib was well tolerated and demonstrated clinical activity against advanced RET-rearranged NSCLCs, suggesting its potential role in this specific subset of malignancies. Clinical trials addressing its efficacy and the optimal dosing schedule in the present context are underway, and results are eagerly awaited.

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

“…Lenvatinib, another TKI, yielded only limited clinical activity (ORR 16%) in a phase II trial [237]. Alectinib showed response in patients with pretreated RET-positive NSCLC in two small case series [238,239]. The phase I/II ALL-RET study failed to demonstrate convincing activity of alectinib [240].…”

Case report: Recurrent lung infections following treatment with pralsetinib for an elderly patient with RET-fusion positive NSCLC

“…At that time, there were no targeted therapies approved or available for the treatment of RET-fusion positive NSCLC in the mainland China. In a previous case series study of patients with NSCLC with RET-fusion, alectinib demonstrated clinical activity and good tolerance (12). On the Basis of this information, the patient was treated with alectinib as first-line treatment, which was administered orally at a dose of 600 mg twice daily since November 15, 2020.…”

Targeted therapy of RET fusion-positive non-small cell lung cancer

“…Ribeiro et al. ( 93 ) investigated the efficacy and tolerability of alectinib in four patients with RET fusion-positive NSCLC who received 600 mg twice daily. All patients had previous chemotherapy and TKI therapy.…”