Trastuzumab

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) in combination with pertuzumab has been approved in the European Union (EU) for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency and is based on results from the DESTINY-Breast09 phase 3 trial. The results were presented at the 2025 American Society of Clinical Oncology Annual Meeting and subsequently published in The New England Journal of Medicine . Cristina Saura, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, steering committee member and investigator for the DESTINY-Breast09 trial, said: “For patients diagnosed with HER2-positive metastatic breast cancer, maintaining disease control for as long as possible in the first-line setting is a critical treatment goal. The combination of trastuzumab deruxtecan and pertuzumab represents a significant therapeutic advance, with progression-free survival exceeding three years compared to approximately two years with the current standard of care, and has the potential to become the new first-line standard of care.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “This approval brings Enhertu to patients in the EU earlier in the course of their metastatic disease and sets a new benchmark for progression-free survival in the first-line setting. HER2-positive metastatic breast cancer is an aggressive disease, so to give patients the best chance of improving long-term outcomes, it is critical to initiate effective HER2-directed therapy early and continue treatment for as long as patients benefit.” Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: “This milestone marks the second new indication for Enhertu in the EU in just two months following the recent tumour agnostic approval. This approval of Enhertu in combination with pertuzumab has the potential to reshape clinical practice in the first-line treatment setting for patients with HER2-positive metastatic breast cancer.” In DESTINY-Breast09, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% versus ataxane, trastuzumab and pertuzumab (THP) in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Median progression-free survival (PFS) was 40.7 months with Enhertu in combination with pertuzumab compared to 26.9 months with THP. Following this approval in the EU, Daiichi Sankyo is due to received a milestone payment of $100m from AstraZeneca for the first-line unresectable or metastatic HER2-positive breast cancer indication.

Jazz Pharmaceuticals has added a second overall survival win to Ziihera’s cap, bolstering the bispecific’s claim as the new HER2 agent of choice in stomach cancer. On the heels of a broad FDA approval for first-line HER2-positive gastroesophageal adenocarcinoma (GEA), the phase 3 trial supporting Ziihera’s recent nod reported meeting the overall survival endpoint in another comparison. This time, Ziihera plus chemo showed a statistically significant and clinically meaningful improvement in OS compared with trastuzumab (Herceptin) plus chemo during the second interim analysis of the Herizon-GEA-01 trial, Jazz announced Monday. Previously, Ziihera’s combination with BeOne Medicines’ PD-1 inhibitor Tevimbra and chemo delivered a positive OS readout at the first interim analysis with a 28% improvement over the trastuzumab-chemo duo. At that time, the Ziihera-chemo combo posted a favorable trend toward a 20% death-risk reduction, which didn’t pass the statistical significance threshold. Now, the magnitude of improvement has improved for both Ziihera regimens, either with or without Tevimbra, according to Jazz. “These results reinforce our confidence that Ziihera is the new HER2-targeted backbone therapy in first-line HER2+ advanced GEA, replacing trastuzumab and extending survival beyond the current standard of care,” Jazz’s R&D chief, Rob Iannone, M.D., said in an Aug. 31 statement. The FDA approved Ziihera to expand into HER2-positive GEA on Aug. 25. Following the approval, citing clinical data and potential to expand Ziihera’s development program, Jazz increased its peak sales projection of the HER2 bispecific antibody to a range between $3 billion and $5 billion, up from the previous $2 billion-plus target. The latest FDA nod came with an unexpected black box warning about diarrhea adverse events, including life-threatening cases. However, analysts mostly viewed the safety issue as manageable given the relatively low discontinuation rate in the Herizon-GEA-01 trial. The FDA label for the Ziihera-Tevimbra-chemo regimen covers tumors with HER2 expressions at IHC 3+ and IHC 2+/ISH+ , while the Ziihera-chemo doublet is limited to patients with IHC 3+ only. During a call with analysts on Aug. 25, Jazz’s chief commercial officer, Samantha Pearce, said that the company believes that Ziihera-Tevimbra-chemo is the “preferred choice” for all indicated patients, except those to whom Tevimbra may be contraindicated. While the second OS readout would be interesting to see, Jazz’s commercial focus will be on the Tevimbra-including triplet, she said on the call. Based on the FDA label, Jefferies analysts have put Ziihera’s peak sales potential in first-line GEA at more than $1.5 billion, while Leerink Partners analysts suggest the drug could reach $2.7 billion in the indication. GEA includes cancers of the stomach, gastroesophageal junction and esophagus and is the fifth most common cancer worldwide. About 20% of patients have HER2-positive disease, which translates into about 8,000 U.S. cases per year, according to Jazz. For Ziihera, the company said that about 3,000 to 4,000 patients in the U.S. are eligible to receive treatment in the first-line, unresectable disease setting and are tested for HER2.