Outcomes of switching from crizotinib to alectinib in patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase fusion

Abstract

Background: Alectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion. However, the therapeutic efficacy and side effects are still largely unknown of patients who switched to next-generation ALK tyrosine kinase inhibitors (ALK-TKIs), such as alectinib, after experiencing no disease progression with initial crizotinib treatment.Methods: This prospective real-world study enrolled patients who were treated with alectinib after experiencing no disease progression with initial crizotinib treatment. The patients' baseline characteristics, objective response rate (ORR) of crizotinib and alectinib, size change of target tumor lesions, treatment regimen and adverse events (AEs) were collected and analyzed.Results: The study included 53 patients, the majority of whom (96.2%) had non-squamous NSCLC.The median age was 51 (range, 31-80) years old. The ORR of first-line crizotinib was 54.7%. The ORR of sequential alectinib was 73.6%, and 90.5% of patients showed further tumor shrinkage after the alectinib treatment. The median progression-free survival was not reached, and 90.5% of patients were still enrolled in the study at the last follow-up. Among them, 34.0% of patients switched to alectinib treatment due to the toxicity. Crizotinib was associated with a higher frequency of AEs of grades 3 and 4 than alectinib (15.1% vs. 0%). Neither group had any AEs resulting in death.Conclusions: Switching to alectinib might be an option for patients who do not experience disease progression with initial crizotinib therapy, and may promote better treatment compliance.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study

“…A prospective study confirmed that such patients still experience significant therapeutic benefits (10).…”

“…Some ALK -positive NSCLC patients are unable to tolerate the adverse reactions of crizotinib, thus, requiring a switch to alectinib. A prospective study confirmed that such patients still experience significant therapeutic benefits ( 10 ).…”

Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical

“…Furthermore, it has exhibited remarkable effectiveness against several novel ALK fusion proteins, including VKORC1L1–ALK [ 91 ], SQSTM1–ALK [ 92 ], HIP1–ALK [ 93 ] and STRN–ALK [ 94 ]. For patients whose disease progression persists despite initial treatment with Crizotinib, converting to Alectinib may be a viable option that could enhance treatment compliance [ 95 ]. Patients undergoing Alectinib treatment commonly exhibit elevated levels of creatinine phosphokinase and may experience neutropenia [ 79 ].…”

Targeting ALK Rearrangements in NSCLC: Current State of the Art

“…In a final analysis of the J-ALEX study, compared to crizotinib, alectinib did not achieve overall survival (OS) benefit ( 60 ), reflecting that the crossover to the post first-line treatment might greatly influence OS, especially in ALK+ NSCLC who could get significant benefit from all ALK TKIs. A prospective real-world study investigated the strategy of switching to alectinib in ALK+ NSCLC patients that did not experience disease progression with initial crizotinib ( 61 ). The results indicated that an early switch from crizotinib to alectinib might be a viable option and may promote better treatment compliance.…”