2023 World Conference on Lung Cancer (Posters)-P2.10. ALKTERNATE: A Pilot Study Alternating Lorlatinib with Crizotinib in Patients with ALK+ NSCLC and ALK-inhibitor Resistance

P2.10. ALKTERNATE: A Pilot Study Alternating Lorlatinib with Crizotinib in Patients with ALK+ NSCLC and ALK-inhibitor Resistance - PDF(Abstract)

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The study, titled "ALKTERNATE: A Pilot Study Alternating Lorlatinib with Crizotinib in Patients with ALK NSCLC and ALK-inhibitor Resistance," aimed to investigate the effectiveness of alternating targeted therapies in patients with ALK gene rearranged non-small cell lung cancer (NSCLC) who had developed resistance to ALK inhibitors.<br /><br />The researchers conducted an open-label translational study in which patients who had progressed on second-generation ALK inhibitors were treated with alternating lorlatinib and crizotinib. The study included 15 patients, of whom 12 proceeded to alternating therapy after achieving disease control with induction lorlatinib.<br /><br />The results showed that the median time to treatment failure was 13 months, with a progression-free survival of 6.1 months for all patients and 10.1 months for those who underwent alternating therapy. The overall response rate was 60%, and the median overall survival was 23 months, with 29 months in patients who underwent alternating therapy.<br /><br />The study also analyzed circulating tumor DNA (ctDNA) samples and found that patients with cleared or reduced ctDNA at 6 months after one cycle of alternating therapy had a longer progression-free survival compared to those with non-clearance. The study identified various genomic variants in patient plasma samples, including compound ALK mutations and co-occurring bypass variants such as EGFR and MYC amplification.<br /><br />The most common toxicities observed were hypercholesterolemia (associated with lorlatinib), diarrhea, nausea (associated with crizotinib), and fatigue, all of which were low grade. The study concluded that alternating lorlatinib and crizotinib is safe, preserves quality of life, and has similar survival outcomes compared to historical data. Further research exploring this novel treatment approach is recommended.<br /><br />In summary, this pilot study investigated alternating targeted therapies in patients with ALK NSCLC and ALK-inhibitor resistance. The results showed promising outcomes in terms of progression-free survival and overall survival, and identified potential resistance mechanisms through ctDNA analysis.

Asset Subtitle

Malinda Itchins

Meta Tag

Speaker Malinda Itchins

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

ALKTERNATE

lorlatinib

crizotinib

ALK NSCLC

ALK-inhibitor resistance

targeted therapies

non-small cell lung cancer

progression-free survival

overall survival

ctDNA analysis