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Enhertu Approved in Singapore for Previously Treated HER2-Positive Advanced Breast and Gastric Cancer

AstraZeneca delivers promising new treatment, one of the fastest-developed biologics in oncology, to address the high unmet need for third-line treatment.

Enhertu (trastuzumab deruxtecan) has been approved in Singapore for the treatment of late-stage HER2-positive breast and gastric cancer after clinical trials demonstrate that it significantly improves progression-free survival rates for patients with an advanced stage of these more aggressive types of cancers. Singapore Health Science Authority (HSA) has approved its use in advanced HER2-positive breast cancer for adult patients who have received two or more anti-HER2 regimens in the advanced setting. The approval was also granted for advanced HER2- positive gastric cancer for adult patients who have received two or more prior regimens including a trastuzumab-based regime, AstraZeneca confirmed in February.

Enhertu, a HER2-directed antibody-drug conjugate, jointly developed by AstraZeneca and Daiichi Sankyo, is a transformative HER2-directed agent designed for enhanced efficacy in HER2+ disease.

A significant unmet need remains for HER2-positive advanced breast cancer patients previously treated with two or more HER2-targeted therapies. Current treatment options offer limited benefit with response rates of approximately nine to 14 per cent and progression-free survival of three to eight months in the third-line setting. With the approval of Enhertu in Singapore, advanced breast cancer patients will now have a clear, established standard of care following progression on second-line treatment.

Patients with metastatic HER2 positive gastric cancer with progression following first-line treatment have historically faced poor outcomes, including low response to treatment and rapid disease progression. Enhertu’s approval in Singapore for gastric cancer represents the first time a HER2 directed medicine has demonstrated a significant improvement in survival compared to chemotherapy for patients following initial treatment in the metastatic setting and it has the potential to become the new standard of care for this patient population.

Dr. Vikram Shetty, Medical Director, AstraZeneca Singapore said, “The approval of Enhertu means that we are able to bring the benefits of this medicine to Singaporean patients with previously treated, metastatic, HER-2 positive breast and gastric cancer. The breadth, depth, and durability of response provided by the treatment are already changing the practice and transforming outcomes for these groups of patients around the world, and we are proud that Enhertu is now available for HER2-positive advanced breast and gastric cancer patients with high unmet need in Singapore.”

The approval of Enhertu is based on positive results of two registrational PHASE II trials DESTINY-Breast011 and DESTINY-Gastric014 , which demonstrate significant improvements in tumour control and progression-free survival.

The results from the breast cancer trial showed that Enhertu monotherapy achieved a durable 62 per cent confirmed objective response rate in patients previously treated with two or more anti-HER2 therapies. Additionally, nearly all patients treated with Enhertu, 97.3 per cent, achieved disease control, meaning that their tumours shrank or stop growing during therapy. Enhertu also delivered durable disease control in patients who failed prior antiHER2 therapies, with a sustained 19.4-months of median progression-free survival.

A total of 184 patients who participated in the DESTINY-Breast01 multicentre, single-arm trial received the recommended PHASE II dose of 5.4mg/kg trastuzumab deruxtecan. All patients received prior trastuzumab, trastuzumab emtansine and 66 per cent had prior pertuzumab.

In the DESTINY-Gastric01 trial, patients (n=126) in the Enhertu monotherapy (6.4mg/kg) treatment arm achieved a confirmed objective response rate of 40.5 per cent versus 11.3 per cent, a median overall survival of 12.5 months versus 8.4 months and a median duration of response of 11.3 months versus 3.9 months as compared with chemotherapy. Enhertu also demonstrated a median progression-free survival of 5.6 months compared to 3.5 months with chemotherapy. The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a 41 per cent improvement in survival and a response rate more than three times higher with Enhertu compared to chemotherapy.

In Singapore, breast cancer is the most commonly occurring cancer among women, and gastric cancer is the sixth-seventh leading cause of cancer deaths among both men and women, respectively. Approximately 20 to 25 per cent of breast and gastric cancer patients are identified as HER2-positive.

The safety of Enhertu was evaluated in a pooled analysis from both the Phase II trial DESTINY-Breast01 and the earlier Phase I trial among a total of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu (5.4mg/kg). Based on results from the DESTINY-Breast01 trial, 19 per cent of patients discontinued ENHERTU due to adverse reactions. Enhertu’s safety profile has been consistent and manageable in Phase II DESTINY-Gastric01 trial as well. [APBN]

Source: AstraZeneca