KEY TAKEAWAYS
- DESTINY-Lung01 is a phase 2 trial investigating the efficacy and safety of T-DXd in previously treated HER2-mutated (NSCLC) patients.
- The study aimed to determine the confirmed (ORR) per RECIST v1.1 by (ICR).
- The trial included 91 patients with HER2-mutated NSCLC refractory to standard therapy who received T-DXd 6.4 mg/kg IV Q3W.
- The updated results show a confirmed ORR of 55% (95% CI, 44-65), median PFS of 8.2 months (95% CI, 6.0-11.9), and median OS of 18.6 months (95% CI, 13.8-25.8) in the overall population.
- Drug-related (TEAEs) occurred in 96.7% of patients, with nausea (76.9%), vomiting (47.3%), and alopecia (46.2%) being the most common.
T-DXd (a HER2-targeting antibody-drug conjugate) in patients with previously treated HER2m NSCLC had a confirmed objective response rate (ORR) of 55% (95% CI, 44-65) and a safety profile generally consistent with previous reports in the primary analysis of DESTINY-Lung01 (NCT03505710; data cutoff May 3, 2021). (Li N Engl J Med 2021). This revision includes extended follow-up in all pts and new analyses based on these subgroups. Patients with HER2m NSCLC who did not respond to the first-line treatment were given T-DXd (6.4 mg/kg IV Q3W). The primary endpoint was ORR, measured by independent central review (ICR) using RECIST v1.1. The duration of response (DOR), progression-free survival (PFS), rate of disease control (DCR), overall survival (OS), and safety were considered secondary endpoints. There were 91 patients evaluated for HER2m NSCLC before the data cutoff date of December 3, 2021. 36.3% had asymptomatic CNS met at baseline; 33.0% had received >2 prior therapies; and 94.5%; had previously been treated with platinum-based chemotherapy (CT). The average length of treatment was 6.9 months, and the average length of follow-up was 16.7 months.
Patients with a CNS endpoint achieved are included in the total and subgroup populations shown in the table. Median progression-free survival was 8.2 months (95% CI, 6.0-11.9), median overall survival was 18.6 months (95% CI, 13.8-25.8), median disease-free survival was 10.6 months (5.8-17.7), and DCR was 92.3% (95% CI, 84.8-96.9). Eighty-eight patients (96.7%) experienced drug-related treatment-emergent adverse events (TEAEs). Nausea (76.1%), vomiting (47.3%), and alopecia (46.2%) were the most common TEAEs. Twenty-five patients (27.5%) were diagnosed with drug-induced interstitial lung disease (3 grade [G] 1, 16 G 2, 4 G 3, 2 G 5). Patients with CNS mets and those who had received more than >2 prior therapies both benefited from the long-lasting anticancer effects of T-DXd. T-DXd is safe and effective for patients with HER2m NSCLC who have received prior treatment, and these updated results further support this claim.
Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/phase-ii-trial-of-trastuzumab-deruxtecan-t-dxd-in-patients-pts-with-her2-mutated-her2m-metastatic-non-small-cell-lung-cancer-nsclc-registr
Clinical trail: https://clinicaltrials.gov/ct2/show/NCT03505710
B.T. Li, E.F. Smit, Y. Goto, K. Nakagawa, K. Goto, J. Mazieres, D. Uprety, L. Bazhenova, A. Saltos, E. Felip, J. Pacheco, M. Pérol, L. Paz-Ares, K. Saxena, R. Shiga, Y. Cheng, Q. Yan, D. Planchard, P.A. Jänne/976P – Phase II trial of trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutated (HER2m) metastatic non-small cell lung cancer (NSCLC): Registrational data from DESTINY-Lung01/Annals of Oncology (2022) 33 (suppl_7): S448-S554. 10.1016/annonc/annonc1064
