KEY TAKEAWAYS
- The HERTHENA-Lung01 phase 2 trial aimed to extend safety observations of the HERTHENA-Lung01 trial with 6 months’ additional follow-up for efficacy assessment.
- HER3-DXd showed consistent safety, with hematologic and GI TEAEs mainly occurring in early treatment cycles.
Advanced EGFRm non-small cell lung cancer (NSCLC) requires tolerable therapies for previously treated patients. HERTHENA-Lung01 trial (NCT04619004) demonstrated significant efficacy and manageable safety.
To elaborate on these safety findings further, Hidetoshi Hayashi and the team aimed to present data from an additional 6 months of follow-up.
About 225 patients previously treated with EGFR TKI and platinum-based chemotherapy received HER3-DXd at 5.6 mg/kg IV every 3 weeks.
The median duration of treatment (TX) was 5.5 months (range, 0.7-23.7). Among 224 patients (99.6%), there were any grade (G) treatment-emergent adverse events (TEAEs); 147 (65.3%) experienced G ≥3 events.
The most common any-grade TEAEs included nausea (66.2%), thrombocytopenia (43.6%), and decreased appetite (42.2%). The most common G ≥3 TEAEs were thrombocytopenia (20.9%), neutropenia (19.1%), and anemia (15.1%). GI TEAEs were reported in 88.9% of patients, with 8% experiencing G ≥3 events. The incidence of GI TEAEs generally decreased during treatment.
Two patients (0.9%) had G ≥3 bleeding events unrelated to treatment within ±14 days of experiencing G ≥3 decreased platelet count. Similarly, 2 patients (0.9%) had G ≥3 infections unrelated to treatment within ±14 days of experiencing G ≥3 decreased neutrophil count.
Febrile neutropenia occurred in 7 patients (3.1%; all G ≥3). G-CSF was administered to manage neutropenia in 23 patients (10.2%). The centrally adjudicated treatment-related interstitial lung disease (G 1/2, n=9; G 3, n=4; G 5, n=1) was seen in 14 patients (6.2%); 2 events occurred during the 6-month follow-up period. The median time to onset and duration were 70.5 days (range, 9-474) and 40 days (range, 6-207), respectively.
About 4 patients experienced TEAEs that resulted in death, including pneumonitis, GI perforation, pneumonia, and respiratory failure (one case each). TEAEs leading to dose interruption were observed in 41.3% of patients, dose reduction in 22.2%, and discontinuation in 8.4%. Hematologic AEs occurred early in treatment, were transient, and managed through dose modifications and supportive care.
No patients discontinued treatment due to thrombocytopenia; however, 20 (8.9%) received platelet transfusions. Anemia led to treatment discontinuation in 1 patient (0.4%); 28 (12.4%) received red blood cell transfusions.
The study reported that the HER3-DXd exhibited a manageable safety profile, aligning with prior findings. Hematologic and GI TEAEs generally manifested in initial treatment cycles. No further safety signals were detected.
The trial was sponsored by the Daiichi Sankyo.
Clinical Trial: https://clinicaltrials.gov/study/NCT04619004
Hayashi H, Yu HA, Jänne PAA, et al. (2024) ” Patritumab deruxtecan (HER3-DXd) in previously treated patients (pts) with advanced EGFR-mutated (EGFRm) NSCLC: Updated safety results from HERTHENA-Lung01.” Presented at ELCC 2024. Annals of Oncology (2024) 9 (suppl_3): 1-53. 10.1016/esmoop/esmoop102569 (11P).
