An evaluation of patritumab deruxtecan for the treatment of EGFR-mutated non-small cell lung cancer.

Introduction: Epidermal growth factor receptor (EGFR) mutations represent targetable alterations in non-small cell lung cancer (NSCLC). The treatment landscape in the frontline setting for patients with advanced EGFR-mutated NSCLC is evolving with increasing treatment options. EGFR tyrosine kinase inhibitors (TKIs) have significantly improved outcomes, but resistance inevitably develops, necessitating alternative strategies.

Areas covered: Patritumab deruxtecan is a novel antibody-drug conjugate targeted human epidermal growth factor receptor-3 (HER3), delivering a topoisomerase-I inhibitor payload to HER3-expressing cancer cells. Phase I and II studies have demonstrated efficacy in patients with EGFR-mutant NSCLC with disease progression after prior therapies, including third-generation EGFR TKIs and platinum-based chemotherapy. The phase-II trial reported an objective response rate of 39% and a median progression-free survival of 5.5 months. Patritumab deruxtecan is associated with notable toxicities, including grade 3 and higher hematologic adverse events, gastrointestinal toxicity, and interstitial lung disease (ILD). ILD occurred in 5.3% of patients in the Phase-II study. Early detection and management are crucial for minimizing the risk of complications.

Expert opinion: Patients with advanced EGFR-mutant NSCLC who have received TKI therapy and chemotherapy have limited treatment options. Patritumab deruxtecan demonstrates clinical activity in this population with manageable side effects, addressing an unmet need for patients.