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(Slides)

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The ALKTERNATE study is a pilot study that investigated the efficacy and safety of alternating treatment with the ALK inhibitors lorlatinib and crizotinib in patients with ALK-positive non-small cell lung cancer (NSCLC) who had developed resistance to ALK inhibitors. The study aimed to delay or prevent the development of drug resistance and improve patient outcomes.<br /><br />The study enrolled 15 patients who had progressed on at least one line of second-generation ALK inhibitors. The primary outcome measure was time to treatment failure with alternating ALK inhibitor therapy. Secondary measures included progression-free survival, overall survival, and objective tumor response rate.<br /><br />The results showed that the median time to treatment failure was 13 months, and the median progression-free survival was 6.1 months. The objective response rate was 50%. The study also found that patients who had clear plasma circulating tumor DNA at diagnosis and/or after one cycle of alternating therapy had a median progression-free survival of 24 months, compared to 5.9 months in those who did not clear.<br /><br />The study demonstrated that alternating therapy with lorlatinib and crizotinib was well-tolerated, with no grade 4 or 5 toxicities encountered. The most common adverse events were grade 1 toxicities such as weight gain and peripheral edema.<br /><br />Patient-reported outcomes, including quality of life and mood scores, were maintained or improved on alternating therapy. However, cognitive impairment was observed in 11 out of 12 patients, which fluctuated during the study.<br /><br />Plasma biomarker analysis showed the presence of ALK resistance mutations and other non-ALK mutations in the patients. The study also identified differentially abundant plasma proteins that could potentially serve as biomarkers for treatment response and resistance.<br /><br />Overall, the ALKTERNATE study demonstrated the feasibility and safety of alternating ALK inhibitor therapy in patients with ALK-positive NSCLC. The results support further exploration of this novel treatment approach, including personalized selection of alternating drugs based on real-time circulating tumor DNA analysis.

Asset Subtitle

Malinda Itchins

Meta Tag

Speaker Malinda Itchins

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

ALKTERNATE study

pilot study

alternating treatment

ALK inhibitors

drug resistance

progression-free survival

plasma circulating tumor DNA

toxicities

patient-reported outcomes

biomarkers