2022 World Conference on Lung Cancer (Posters)-P2.14-02. TP53 Mutations Affect Sensitivity to Lorlatinib in ROS1 Positive NSCLC: Final Results of the PFROST Trial

P2.14-02. TP53 Mutations Affect Sensitivity to Lorlatinib in ROS1 Positive NSCLC: Final Results of the PFROST Trial

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The final results of the PFROST trial, which evaluated the use of lorlatinib in crizotinib-refractory ROS1 non-small-cell lung cancer (NSCLC), were presented. The trial included 22 patients who were treated with lorlatinib until disease progression. The overall response rate (RR) was 40%, with a median progression-free survival (PFS) of 8.9 months and median overall survival (OS) not yet reached.<br /><br />The study analyzed the molecular characteristics of the patients to understand the impact on lorlatinib's activity. Among the patients, 15 had baseline brain metastases (BM) and 7 did not. In patients with BM, the median PFS and OS were 8.5 months and 30.4 months, respectively. In patients without BM, the median PFS and OS were 12.6 months and 34.2 months, respectively. The most common pattern of relapse in patients with BM was extracranial failure.<br /><br />The study also identified mutations in the TP53 gene in 11 patients, including 4 cases with concomitant ROS1 mutation. These patients showed a lower response rate (27.3%) and shorter median PFS (8.5 months) and OS (14.6 months) compared to patients without TP53 mutations. This suggests that TP53 mutations identified a subset of ROS1 individuals at a higher risk of disease progression and death.<br /><br />The study concludes that different or more aggressive treatment strategies should be investigated for this specific population with TP53 mutations. The findings highlight the importance of molecular events in modulating the activity of lorlatinib in ROS1 NSCLC and provide insights for personalized treatment approaches.

Asset Subtitle

Lorenza Landi, Italy

Meta Tag

Speaker Lorenza Landi, Italy

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapeutics

Keywords

PFROST trial

lorlatinib

crizotinib-refractory

ROS1 non-small-cell lung cancer

overall response rate

progression-free survival

overall survival

baseline brain metastases

TP53 gene mutations

personalized treatment approaches