2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12B.14 Platinum-Pemetrexed Chemotherapy and Lorlatinib Combination in Advanced ALK Positive NSCLC Progressing to Lorlatinib: A Case Series

EP.12B.14 Platinum-Pemetrexed Chemotherapy and Lorlatinib Combination in Advanced ALK Positive NSCLC Progressing to Lorlatinib: A Case Series

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This case series investigates the effectiveness and safety of combining platinum-pemetrexed chemotherapy (PT/pem-based-CT) with lorlatinib in treating patients with advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) who have progressed on lorlatinib. Lorlatinib is a third-generation ALK tyrosine kinase inhibitor (TKI) used post-failure of earlier generation TKIs, with treatment options limited after lorlatinib resistance.<br /><br />The study retrospectively evaluated six patients treated at the CRO IRCCS, Aviano, Italy, between June 2020 and November 2023. The patients had received an average of two prior ALK-TKIs before lorlatinib and exhibited multifocal progression, including in the lymph nodes, lungs, liver, and brain.<br /><br />The analysis showed that the combination therapy was active in 5 out of 6 patients, resulting in partial response (PR) in two patients and stable disease (SD) in three. One patient showed systemic progression as the best response. The median progression-free survival (mPFS) was 5.5 months, and intracranial mPFS was 7.7 months. Notably, there was only one case of brain metastasis progression during the treatment. <br /><br />Half of the patients required dose reductions due to adverse effects like hypercreatininemia and increased transaminase levels, although no lorlatinib dose reduction was needed. Importantly, liquid biopsies found no ALK resistance mutations during the combination therapy, indicating an unknown resistance mechanism to lorlatinib.<br /><br />While limited by its small scale and retrospective nature, this study suggests potential for the PT/pem-based-CT and lorlatinib combination to manage resistance in ALK-positive NSCLC, but further research is required to establish efficacy and optimize treatment protocols.

Asset Subtitle

Elisa Bertoli

Meta Tag

Speaker Elisa Bertoli

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

platinum-pemetrexed chemotherapy

lorlatinib

ALK-positive NSCLC

anaplastic lymphoma kinase

progression-free survival

brain metastasis

ALK resistance mutations

tyrosine kinase inhibitor

retrospective study

liquid biopsy