Dong-Wan Kim scholars from the Seoul National University Hospital in South Korea will give an oral report on the special meeting of metastatic non-small cell lung cancer at the 52nd Annual Meeting of the American Society of Oncology (ASCO) in Chicago on June 6, 2016 local time: the first report An important randomized phase II clinical trial of the efficacy and safety of using Brigatinib (BRG) in patients with ALK + crizotinib-resistant non-small cell lung cancer (NSCLC).
BRG is an oral tyrosine kinase inhibitor (TKI) in the observation period. It has preclinical activity against ALK rearrangements and CRZ-resistant mutations. This clinical phase 1/2 trial shows good prospects for BRG. Both BRG’s response rate and AEs can vary with the starting dose, therefore, in this ongoing randomized study, two BRG use options were evaluated.
The results of this study show that BRG has a clear response to treatment, stable PFS, and acceptable safety characteristics. Therefore, they plan to conduct a phase III clinical trial comparing CRZ BRG 90 mg qd * 7 days and 180 mg qd in patients with ALK + advanced NSCLC and CRZ in patients who have not used TKI.
In this trial, patients ≥ 18 years of age, ALK + NSCLC progressed after using CRZ and no other ALK TKI patients were available. According to whether the patient has a baseline condition of intracranial metastasis and the best response to the previous use of CRZ, the patients were randomly divided into 1: 1 oral BRG 90 mg qd (group A) or 90 mg qd x 7d and 180 mg qd (B group).
The primary endpoint is observation-assessment-confirmation of ORR per RECIST v1.1. Key secondary endpoints include PFS and IRC to assess formal ORR and CNS responses. 222 patients were randomly divided into A / B group, n = 112 / n = 110. As of September 21, 2015, the last patient was included. The average age was 51/57 years old, and 71% / 67% had brain metastases.
The proportion of patients in groups A and B was 63% / 74% while the experiment was still in progress on December 7, 2015, and the average duration of treatment was 25 weeks / 23 weeks. Observation-assessment of group A: 46% of confirmed ORR (39 confirmed reactions + 12 single responses waiting to be confirmed), including 1 confirmed complete response (CRs); ORR of group B: 54% (49 confirmed reactions) + 10 responses awaiting confirmation), including 5 confirmed CRs. The median PFS for A / B is 8.8 months / 11.1 months.
Toxic events in group A / B were 44/25, the most common emergency treatment AEs of grade ≥ 3, group A / B included: increased CPK (3% / 8%), hypertension (4% / 5%), Lung infection (3% / 5%), rash (1% / 4%), elevated blood lipids (3% / 2%) and pneumonia (2% / 3%). In 6% of patients, pulmonary events occurred at an early stage (3% ≥ grade 3 within 7 days of initiation of treatment); this event was not seen in group B and increased to 180 mg within 7 days of initiation of treatment and thereafter. The interruption and reduction of A / B group due to AEs were 3% / 6% and 7% / 18%, respectively.
