EU green light to a earlier use of trastuzumab deruxtecan, drug-conjugated monoclonal antibody (Adc) by Daiichi Sankyo and AstraZeneca, in the treatment of metastatic breast cancer Her2-positive (Her2 +). The ‘smart’ therapy, specifically designed to target the Her2 receptor, has achieved the extension of the indication as monotherapy for adult patients with unresectable or metastatic Her2 + breast cancer who have received one or more previous regimens of anti-Her2.
L’European Commission approval – explains a note from the two pharmaceutical companies – follows the positive opinion of the Committee for Medicinal Products for Human Use (Chmp) of the European Medicines Agency Ema, and is based on the results of the phase 3 study Destiny-Breast03, published in ‘The New England Journal of Medicine ‘, in which trastuzumab deruxtecan demonstrated a 72% reduction in the risk of disease progression or death compared to T-Dm1 (trastuzumab emtansine), in patients with unresectable and / or metastatic Her2 + breast cancer previously treated with trastuzumab and taxane. Median progression-free survival for patients treated with trastuzumab deruxtecan was not achieved, while that with T-Dm1 was 6.8 months, according to blinded independent central review.
In Europe, more than 530,000 cases of breast cancer are diagnosed each year, about a fifth of which is considered Her2 +. Despite initial treatment with trastuzumab, pertuzumab and taxane, patients with Her2 + metastatic breast cancer often experience disease progression. “This approval represents an important milestone for European patients and clinicians, as patients previously treated for Her2-positive metastatic breast cancer with current standard treatment usually progress in less than a year,” he says. Javier Cortés, Head of the International Breast Cancer Center (IBCC) in Barcelona, Spain – In the Destiny-Breast03 study, the time to progression extended well beyond one year for patients who received trastuzumab deruxtecan, demonstrating the potential of this drug to become a new benchmark in the treatment of Her2 + metastatic breast cancer “.
Further results of the Destiny-Breast03 trial – the note details – showed that, in the analysis of the secondary endpoint of overall survival, a strong signal of improvement was found with trastuzumab deruxtecan, although this analysis is not yet mature and is in progress. course a further follow-up. Almost all patients treated with trastuzumab deruxtecan were alive at 9 months, compared with 91.3% of patients treated with T-Dm1. The confirmed objective response rate was more than double in the trastuzumab deruxtecan arm compared to the T-Dm1 arm.
The safety profile of trastuzumab deruxtecan was evaluated in a pooled analysis of 573 patients with different tumor types who had received at least one dose of treatment in clinical trials. The median duration of trastuzumab deruxtecan therapy was 11.3 months. The most common adverse reactions were nausea (77%), fatigue (57.2%), vomiting (46.8%), alopecia (38%), neutropenia (34.6%), constipation (33.9%) , decreased appetite (33.7%), anemia (32.3%), diarrhea (30.7%), musculoskeletal pain (27.4%), increased transaminases (24.4%), leukopenia (24 , 1%), thrombocytopenia (23%) and upper respiratory tract infection (22.7%). Cases of interstitial lung disease (Ild) or pneumonia were reported in 12.0% of patients. Most cases of Ild were grade 1 (2.6%) or 2 (7.3%). Grade 3 cases occurred in 0.7% of patients, with no Grade 4 cases, and Grade 5 cases in 1.4% of patients.
Based on the Destiny-Breast03 results – Daiichi and AZ highlight – the ESMO (European Society of Medical Oncology) guidelines in clinical practice were updated in October 2021 to recommend the use of trastuzumab deruxtecan as preferable second-line therapy for patients with Her2 + metastatic breast cancer, progressing after taxane and trastuzumab therapy. As part of this approval, the EC also extended the market protection period for trastuzumab deruxtecan in this setting by an additional year, based on the significant clinical benefit over existing approved therapies.
“We believe there is a significant need in Europe to transform clinical outcomes for patients with Her2-positive metastatic breast cancer,” said Ken Keller, Global Head Oncology Business, President and CEO of Daiichi Sankyo. treatment with trastuzumab deruxtecan demonstrated superior progression-free survival and double the response rate compared to another anti-HER2 ADC, and with this extension of indication we are now able to offer patients with Her2 + metastatic breast cancer a another therapeutic option at an earlier stage of their treatment path “.
“Thanks to this approval – adds Dave Fredrickson, Executive Vice President, Oncology Business Unit of AstraZeneca – in Europe patients with Her2 + metastatic breast cancer will have the opportunity to be treated with this drug at an even earlier stage of therapy, increasing thus the possibilities for better clinical outcomes, in addition to those we can already offer in more advanced stages. This milestone represents an important step towards achieving our vision of continuing to offer the transformative potential of trastuzumab deruxtecan as soon as possible in the treatment of patients, in order to improve the outcomes of the disease “.