In a nutshell
The study compared the effectiveness and safety of trastuzumab deruxtecan (TD; Enhertu) with trastuzumab emtansine (TE; Kadcyla) in patients with HER2-positive (HER2+) metastatic breast cancer (BC). The study found that TD was more effective and well-tolerated compared to TE in these patients.
Some background
HER2+ BC tests positive for human epidermal growth factor 2 (HER2). This protein is found on BC cells that helps BC cells grow quickly. About 15%-20% of BCs consist of this protein. The current treatment for HER2+ metastatic BC is a combination of surgery, chemotherapy, hormone therapy, and targeted cancer drugs.
The first line of treatment for HER2+ metastatic BC is pertuzumab (Perjeta) and trastuzumab (Herceptin) combined with a taxane chemotherapy. The second line of treatment is trastuzumab deruxtecan (TD) or trastuzumab emtansine (TE).
TD and TE are HER2+ targeted antibody-drug conjugates. They work by binding the trastuzumab molecule to the HER2 protein on cancer cells, while the conjugate molecule (deruxtecan and emtansine) attacks and kills cancer cells. Past short-term studies have shown an improvement in progression-free survival in patients with HER2+ metastatic BC with TD compared to TE. However, the longer-term effectiveness and safety profile of both drugs have not been explored.
Methods & findings
The study involved 524 patients with advanced HER2+ BC. They were randomly assigned to either TD (261) or TE (263). The average duration of study follow-up was 28.4 months with TD and 26.5 months with TE.
79% of the TD group had a response to treatment compared to 35% in the TE group. In the TD group,21% of patients had a complete response (complete disappearance of cancer) and 57% had a partial response (tumor shrinkage). In the TE group, 10% of patients had a complete response and 25% had a partial response.
The average survival without cancer worsening was 28.8 months with TD and 6.8 months with TE. Patients treated with TD were 67% more likely to survive without cancer worsening compared to those treated with TE.
After 1 year, 75.2% of patients in the TD group were alive without cancer worsening compared to 33.9% in the TE group. After 2 years, 53.7% of patients in the TD group were alive without cancer worsening compared to 26.4% in the TE group.
Patients in the TD group were 36% more likely to have a better overall survival compared to those in the TE group. 94.1% of patients in the TD group were alive after 1 year compared to 86% in the TE group. After 2 years, 77.4% of patients in the TD group were alive compared to 69.9% in the TE group.
The number of serious side effects was similar in both groups (56% in the TD group and 52% in the TE group). The most common side effects were pneumonitis (inflammation of lung tissue), interstitial lung disease, and pneumonia in the trastuzumab deruxtecan group. In the trastuzumab emtansine group, the most reported side effects were thrombocytopenia (low platelet counts) and pneumonitis.
The bottom line
The study concluded that trastuzumab deruxtecan was more effective than trastuzumab emtansine in patients with advanced HER2+ BC.
The fine print
The enrolment of patients was mostly from Asia and does not reflect the general population. This study was funded by Daiichi Sankyo and AstraZeneca, the manufacturers of TD.
Published By :
Lancet (London, England)
Date :
Dec 06, 2022
