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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Alectinib
M Herden1, Cornelius F Waller2
1Department of Haematology, Oncology and Stem Cell Transplantation, University Medical Centre Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Abstract:
Alectinib is an ATP-competitive small molecule and a second-generation inhibitor of ALK. EML4-ALK rearrangement is found in 3-5% of patients with NSCLC. The first-generation inhibitor crizotinib has changed the treatment dramatically, though most of the patients show disease progression within one year. Extra-thoracic progress, i.e., CNS metastases is common. The second-generation inhibitor alectinib has shown significant improvement in PFS and a remarkable prolongation of time to CNS progression. Alectinib has received approval as first-line therapy as well as second-line therapy after crizotinib failure. The toxicity profile is favorable compared to crizotinib and chemotherapy.
Insights
Alectinib, a second-generation ALK inhibitor, shows improved progression-free survival and delays central nervous system progression in non-small cell lung cancer (NSCLC) patients. It offers a favorable safety profile compared to older treatments.
Area of Science:
- Oncology
- Pharmacology
Background:
- Anaplastic Lymphoma Kinase (ALK) rearrangements occur in 3-5% of non-small cell lung cancer (NSCLC) cases.
- First-generation ALK inhibitors like crizotinib improved treatment but often resulted in disease progression within a year, with frequent central nervous system (CNS) metastases.
- There is a need for more effective therapies with better CNS penetration and longer duration of response.
Purpose of the Study:
- To evaluate the efficacy and safety of alectinib, a second-generation ALK inhibitor.
- To compare alectinib's performance against crizotinib and chemotherapy in NSCLC patients with ALK rearrangements.
- To assess alectinib's impact on progression-free survival (PFS) and time to CNS progression.
Main Methods:
- Alectinib, an ATP-competitive small molecule inhibitor targeting ALK.
- Clinical trials comparing alectinib with crizotinib and chemotherapy in NSCLC patients.
- Assessment of progression-free survival (PFS) and CNS progression events.
Main Results:
- Alectinib demonstrated significant improvements in PFS compared to previous treatments.
- Alectinib showed a remarkable prolongation in the time to CNS progression.
- Alectinib was approved for both first-line and second-line therapy after crizotinib failure.
- The toxicity profile of alectinib was found to be favorable.
Conclusions:
- Alectinib represents a significant advancement in the treatment of ALK-rearranged NSCLC.
- Its efficacy in controlling systemic and CNS disease, coupled with a favorable safety profile, makes it a preferred therapeutic option.
- Alectinib offers improved outcomes for NSCLC patients with ALK alterations.
