2023 World Conference on Lung Cancer (Posters)-P2.10. Updated Survival Data in Advanced ALK-rearranged Non-small Cell Lung Cancer Treated with Alectinib and Bevacizumab in the ALEK-B Study

P2.10. Updated Survival Data in Advanced ALK-rearranged Non-small Cell Lung Cancer Treated with Alectinib and Bevacizumab in the ALEK-B Study - PDF(Slides)

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The ALEK-B study investigated the combination of alectinib and bevacizumab as a first-line treatment for advanced ALK-positive NSCLC. The study found that the combination therapy was safe and feasible, and resulted in prolonged progression-free survival (PFS) and prevented early systemic and central nervous system (CNS) progression events. The combination also delayed the appearance of early resistance mechanisms, leading to a higher proportion of patients without progression at the 24-month follow-up compared to historical data. The combination therapy also resulted in profound and durable systemic and intracranial responses in almost all participants. The study suggests that further investigation, ideally a phase III trial including biomarker analysis, is warranted.<br /><br />The primary endpoint of the study was investigator-assessed PFS. At the data cut-off, the median PFS was not reached, with a 24-month PFS of 80.8%. Different variants of the EML4-ALK fusion had varying PFS rates, with variant 3 showing the best outcomes. The presence of homozygous CDKN2A/B loss was significantly associated with worse PFS.<br /><br />The overall response rate was 100%, with 87.8% achieving a partial response and 12.2% achieving a complete response. A profound tumor response, defined as a reduction of 80% or more, was achieved in 58.5% of cases. The combination therapy showed efficacy in both patients with measurable CNS disease and those without brain metastases at diagnosis.<br /><br />The combination of alectinib and bevacizumab was generally well-tolerated, with manageable adverse events. Dose reductions and treatment interruptions were reported in a small number of patients, mainly due to proteinuria and elevated liver enzyme levels.<br /><br />In conclusion, the ALEK-B study demonstrated that the combination of alectinib and bevacizumab is a promising therapeutic option for ALK-positive NSCLC. The combination therapy showed significant efficacy in terms of PFS and overall response rates, with a favorable safety profile. Further investigation is needed to validate these findings and identify potential biomarkers for patient selection.

Asset Subtitle

Oscar Arrieta

Meta Tag

Speaker Oscar Arrieta

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

ALEK-B study

alectinib

bevacizumab

first-line treatment

progression-free survival

resistance mechanisms

intracranial responses

EML4-ALK fusion

overall response rate

biomarkers