ARE ALECTINIB-INDUCED MYALGIA AND ELEVATION CREATINE PHOSPHOKINASE PREDICTORS OF HIGH RECURRECCE-FREE SURVIVAL?

Abstract

Introduction. One in eight cases and one in five deaths are related to lung cancer. Due to high heterogeneity, lung cancer often has an unfavorable prognosis. Approximately 3–5% of patients with non-small cell lung cancer (NSCLC) have an anaplastic lymphoma kinase (ALK) gene rearrangement. Patients with stage I, II, or III lung cancer are undergoing surgery and adjuvant platinum-based chemotherapy. However, the five-year risk of recurrence and death ranges from 45% for patients with stage IB to 76% for patients with stage III. In addition, during adjuvant chemotherapy, 66% of patients experience grade 3 and 4 adverse events. Research rationale.  ALK-positive patients require targeted alectinib therapy. Alectinib is a highly selective second-generation TKI approved by the FDA for treating locally advanced and metastatic NSCLC. Several clinical trials have compared the efficacy and safety of alectinib with other TKIs (crizotinib, ceritinib) and platinum-based chemotherapy. The survival of patients taking alectinib is significantly higher than chemotherapy. In this case report, we would like to describe the development of alectinib-induced myalgia and creatine phosphokinase (CPK) elevation and evaluate their association with recurrence-free survival. Materials and methods. We collected laboratory results and clinical data of a patient with stage IIIA of ALK-positive NSCLC who received adjuvant therapy with alectinib at 600 mg daily for 24 months. The results. Four weeks after alectinib treatment, a biochemistry test showed a grade 1 CPK. After 12 weeks of alectinib treatment, the patient complained of severe muscle pain and weakness. The level of CPK increased three times and corresponded to 2 grades of severity. Targeted therapy was temporarily discontinued. The patient did not take alectinib for ten days. Myalgia symptoms were improved, so the patient continued the alectinib in the previous dose. Moderate myalgia continued for four months. Long-term follow-up after completion of treatment continues for five years and four months. No recurrence of the disease was registered. Discussion. According to the scientific literature data, the mechanism of increasing CPK and the development of myalgia remains unknown. There are assumptions that the cause of myalgia may be inflammation in the muscles. In the ALEX clinical trial, myalgia was a reasonably common side effect of alectinib. 17.1% of patients reported pain, tenderness, or muscle weakness. However, in most cases, the symptoms were moderate, and only 3.3% of patients corresponded to 2 grades of severity. 76% of patients with stage III have a recurrence of the disease within a five-year period. The recurrence-free period of our patient lasts five years and four months. It can be assumed that the treatment results of this patient are satisfactory. Grade 2 myalgia and grade 2 CPK are potential predictors of good response to treatment and high recurrence-free survival. Patients taking alectinib should be warned about the possible appearance of myalgia already within the first month after the start of targeted therapy. Biochemistry test must include CPK. In most cases, there is a direct relationship between the level of CPK and the manifestations of myalgia. Conclusions. Severe myalgia and grade 2 elevation of CPK are likely predictors of five-year recurrence-free survival in patients with completely resected NSCLC treated with adjuvant alectinib therapy.