Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer

Trastuzumab deruxtecan: An antibody-drug conjugate embracing its destiny in breast cancer

“… In DESTINY-Breast 03, Trastuzumab Deruxtecan, a HER2-specific antibody-drug conjugate, proved superior to T-DM1 in patients with HER2+ metastatic breast cancer progressing on taxane and trastuzumab. 1 This study supported its recent approval as second-line therapy in HER2+ metastatic breast cancer. …”

“…One such ADC, fam- trastuzumab deruxtecan (T-DXd), has recently been shown to prolong PFS compared with trastuzumab emtansine (T-DM1) in HER2+ MBC in the international phase 3 randomized clinical trial DESTINY-Breast 03 (DB-03), the focus of this spotlight, reported by Cortés et al. 1 …”

“…In DB-03, there were only 0.8% G3 events and no ILD-related deaths. 1 Additional frequent toxicities noted with T-DXd in DB-03 included high rates of G ≥ 3 myelosuppression (including neutropenia [19%], anemia [5.8%], thrombocytopenia [7.8%]), nausea (6.6%), and fatigue (5.1%), a reminder that off-target toxicity remains a challenge for the “targeted” chemo approach of ADCs.…”

Systemic Treatments for Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Old Certainties and New Frontiers

“… 24 In fact, only 2 cases (0.8%) of grade 3 interstitial lung disease were reported, with no cases of grade 4 and/or 5 toxicities. 24 Several recommendations remain to be considered, including close monitoring for symptoms as well as starting steroids as soon as interstitial lung disease is suspected. 36 , 37 …”

“…The results of this study were previously presented at ESMO 2021 and have been recently published by Cortes and colleagues on the New England Journal of Medicine. 24 Of note, the 12-month PFS rate was 75.8% with trastuzumab deruxtecan vs 34.1% with T-DM1, with a HR for progression or death from any cause of .28 (95% Confidence Interval .22 to .37; P < .001) 24 ; median PFS was not reached for the experimental arm while it was 6.8 months for T-DM1. However, it is worth noting that serious drug-related toxicities were reported in 10.9% of patients treated with trastuzumab deruxtecan (versus 6.1% of patients receiving T-DM1).…”