The positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency is based on the results of two studies, DESTINY-Gastric02 and DESTINY-Gastric01, each of which showed clinically significant efficacy and an improvement in overall survival of trastuzumab-deruxtecan compared to chemotherapy.
November 18 –
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the EU approval of trastuzumab deruxtecan as monotherapy for the treatment of adult patients with adenocarcinoma of the stomach or gastroesophageal junction (GEJ). positive who have previously received trastuzumab-based treatment.
Trastuzumab deruxtecan is a drug-conjugated antibody specifically designed to target the HER2 receptor and is being co-developed and co-commercialized by Daiichi Sankyo and AstraZeneca.
The CHMP based its favorable opinion on the results of the phase 2 studies DESTINY-Gastric02 and DESTINY-Gastric01.
In the DESTINY-Gastric02 study, conducted in patients from North America and Europe, updated results showed that treatment with trastuzumab deruxtecan resulted in a confirmed objective response rate (cORR) of 41.8% (CI). [IC] of 95%: 30.8-53.4) as assessed by an independent central review (ICR). The median duration of response (DoR) was 8.1 months (95% CI: 5.9 – not estimable). The median overall survival (OS) was 12.1 months (95% CI: 9.4-15.4). The primary results of the Phase 2 DESTINY-Gastric02 study were presented at the European Society of Medical Oncology (ESMO) 2021 Congress and subsequently updated at ESMO 2022.
In the DESTINY-Gastric01 study in patients from Japan and South Korea, treatment with trastuzumab deruxtecan resulted in an ORR of 51.3% (95% CI: 41.9-60.5), compared with 14.3% (95 %CI: 6.4-26.2) with chemotherapy (irinotecan or paclitaxel) as assessed by ICR (p<0.0001). The confirmed ORR, one of the key efficacy results, was 42.0% (95% CI: 33.0, 51.4) with trastuzumab deruxtecan compared to 12.5% (95% CI: 5.2-24.1 ) with chemotherapy as assessed by the IKR. Patients treated with trastuzumab deruxtecan also had a 40% reduced risk of death compared to patients treated with chemotherapy (hazard ratio [HR] = 0.60; 95% CI: 0.42-0.86, p=0.01) with a median OS of 12.5 months (95% CI: 10.3-15.2) versus 8.9 months (95% CI: 10.3-15.2) versus 95%: 6.4-10.4). The primary analysis was published in the New England Journal of Medicine, with updated data presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
The recommendation will now be reviewed by the European Commission, which has the power to approve medicines in the EU.
“Trastuzumab deruxtecan is the first anti-HER2 drug to show a significant improvement in overall survival compared to chemotherapy in patients with gastric cancer after initial treatment with an anti-HER2 drug administered at advanced or metastatic stage,” he said. Ken Takeshita, Global Head of Research & Development of Daiichi Sankyo. “The CHMP opinion recognizes the high unmet need in this patient population and brings us one step closer to making this medicine available to European gastric cancer patients.”
“In many European countries, gastric cancer is usually diagnosed at an advanced stage and patients face high mortality rates,” he explains. Susan GalbraithExecutive Vice President of Oncology R&D at AstraZeneca: “If approved, trastuzumab deruxtecan would be the first anti-HER2 drug in more than a decade to target patients in the European Union with advanced gastric cancer.”
In DESTINY-Gastric02, the safety profile observed in patients treated with trastuzumab deruxtecan was consistent with that observed in other studies of this ADC, and no new safety signals were identified. Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 55.7% of patients receiving trastuzumab deruxtecan 6.4 mg/kg. The most common Grade 3 or greater treatment-emergent TEAE occurring in ≥10% of trastuzumab deruxtecan-treated patients was anemia (13.9%). There were eight cases (10.1%) of treatment-emergent interstitial lung disease (ILD) or pneumonitis as determined by an independent review panel. The majority (six) were low grade (Grade 1 or 2), with two reported events of Grade 5 ILD or pneumonitis.
In DESTINY-Gastric01, the safety profile observed in patients treated with trastuzumab deruxtecan was consistent with that observed in other studies of this ADC, and no new safety signals were identified. Grade 3 or higher treatment-emergent adverse events occurred in 85.6% of patients receiving trastuzumab deruxtecan 6.4 mg/kg. The most common Grade 3 or higher treatment-emergent adverse reactions occurring in ≥20% of patients treated with trastuzumab deruxtecan were: neutrophil count decreased (51.2%), anemia (38.4%), and white blood cell count decreased (20.8 %). There were 16 cases (12.8%) of treatment-emergent ILD or pneumonia as determined by an independent review board. The majority (13) were low grade (Grade 1 or 2), with two Grade 3 events and one Grade 4 event. There were no Grade 5 ILD or pneumonitis events.
Trastuzumab deruxtecan is not yet approved in the EU for the treatment of advanced gastric cancer and is subject to additional monitoring.
November 18, 2022
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