Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated human epidermal growth factor receptor 2 (HER2;ERBB2)-mutant (HER2m) metastatic non-small cell lung cancer (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes. Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review. Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 months (8.2-20.7) and 16.5 months (9.4-20.8). cORR (95% CI) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%). Safety profile was acceptable and generally manageable. Median treatment duration (Q1-Q3) was 7.7 months (3.7-14.4) and 8.3 months (2.8-13.1); drug-related grade ≥3 treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease (ILD) occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1/2; one grade 5 in each arm. Health-related quality of life (HRQoL) was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on HRQoL observed at either dose. Conclusions: T-DXd showed strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose showed a more favorable benefit-risk profile, including lower adjudicated drug-related ILD incidence.
Final analysis results and patient-reported outcomes from DESTINY-Lung02-a dose-blinded, randomized, phase 2 study of trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small cell lung cancer
Novello, Silvia;
2025-01-01
Abstract
Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated human epidermal growth factor receptor 2 (HER2;ERBB2)-mutant (HER2m) metastatic non-small cell lung cancer (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes. Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review. Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 months (8.2-20.7) and 16.5 months (9.4-20.8). cORR (95% CI) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%). Safety profile was acceptable and generally manageable. Median treatment duration (Q1-Q3) was 7.7 months (3.7-14.4) and 8.3 months (2.8-13.1); drug-related grade ≥3 treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease (ILD) occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1/2; one grade 5 in each arm. Health-related quality of life (HRQoL) was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on HRQoL observed at either dose. Conclusions: T-DXd showed strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose showed a more favorable benefit-risk profile, including lower adjudicated drug-related ILD incidence.
| File | Dimensione | Formato | |
|---|---|---|---|
|
1-s2.0-S1556086425009815-main.pdf
Accesso aperto
Tipo di file:
PDF EDITORIALE
Dimensione
646.2 kB
Formato
Adobe PDF
|
646.2 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
