Patritumab deruxtecan shows PFS, but no OS-benefit in EGFR-mutant NSCLC

Despite stronger disease control and intracranial activity, patritumab deruxtecan did not outperform chemotherapy in overall survival (OS) in EGFR-mutant advanced or metastatic non-small cell lung cancer (NSCLC).

The phase 3 HERTHENA-Lung02 trial (NCT05338970), presented by Prof. Tony Mok (Chinese University of Hong Kong, China), investigated the potential survival benefits from the HER3-targeting antibody-drug conjugate patritumab deruxtecan (also known as HER3-DXd) compared to platinum-based chemotherapy in participants with epidermal growth factor receptor (EGFR)-mutant advanced or metastatic NSCLC following progression on 1 or 2 prior EGFR tyrosine kinase inhibitors (TKIs; n=586, most of whom had received prior osimertinib) [1].

The median OS was nearly identical in both arms, with 16.0 months with patritumab deruxtecan compared with 15.9 months with chemotherapy (HR 0.98; 95% CI 0.79–1.22). Nevertheless, patritumab deruxtecan offered superior progression-free survival (5.8 vs 5.4 months; HR 0.77; 95% CI 0.63–0.94; P=0.011) and objective response rate (35.2% vs 25.3%) compared with chemotherapy, along with higher intracranial activity. The intracranial response rate was 19.0% vs 11.6%, and intracranial complete responses occurred in 12.4% of participants in the patritumab deruxtecan arm, compared to 4.2% in the chemotherapy arm.

The safety profile of patritumab deruxtecan was consistent with prior experience: grade ≥3 treatment-related adverse events occurred in 58% of participants receiving patritumab deruxtecan, compared to 46% on chemotherapy, with interstitial lung disease reported in 5.2%.

Prof. Mok closed with an outlook on additional ongoing analysis: “Evaluation of the association of biomarkers, including HER3 immunohistochemistry, with efficacy parameters in HERTHENA-Lung02 and their suitability as a predictive biomarker is ongoing.”

1. Mok T, et al. Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study. Abstract #8506, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

Copyright ©2025 Medicom Medical Publishers



Posted on 30 July 2025