Dataset Information

Improving the tolerability of osimertinib by identifying its toxic limit.

ABSTRACT:

Background

Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction.

Methods

In this real-life prospective cohort study, patients with NSCLC treated with osimertinib were followed for severe toxicity (grade ⩾3 toxicity, dose reduction or discontinuation, hospital admission, or treatment termination). Blood for pharmacokinetic analyses was withdrawn during every out-patient visit. Primary endpoint was the correlation between osimertinib clearance (exposure) and severe toxicity. Secondary endpoint was the exposure-efficacy relationship, defined as progression-free survival (PFS) and overall survival (OS).

Results

In total, 819 samples from 159 patients were included in the analysis. Multivariate competing risk analysis showed osimertinib clearance (c.q. exposure) to be significantly correlated with severe toxicity (hazard ratio 0.93, 95% CI: 0.88-0.99). An relative operating characteristic curve showed the optimal toxic limit to be 259 ng/mL osimertinib. A 50% dose reduction in the high-exposure group, that is 25.8% of the total cohort, would reduce the risk of severe toxicity by 53%. Osimertinib exposure was not associated with PFS nor OS.

Conclusion

Osimertinib exposure is highly correlated with the occurrence of severe toxicity. To optimize tolerability, patients above the toxic limit concentration of 259 ng/mL could benefit from a preventive dose reduction, without fear for diminished effectiveness.

SUBMITTER: Agema BC

PROVIDER: S-EPMC9168866 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Improving the tolerability of osimertinib by identifying its toxic limit.

Agema Bram C BC Veerman G D Marijn GDM Steendam Christi M J CMJ Lanser Daan A C DAC Preijers Tim T van der Leest Cor C Koch Birgit C P BCP Dingemans Anne-Marie C AC Mathijssen Ron H J RHJ Koolen Stijn L W SLW

Therapeutic advances in medical oncology 20220603

<h4>Background</h4>Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction.<h4>Methods</h4>In this r ...[more]

PMID: 35677320

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Dataset Information

Improving the tolerability of osimertinib by identifying its toxic limit.

Background

Methods

Results

Conclusion

Publications

Improving the tolerability of osimertinib by identifying its toxic limit.

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