AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in China as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy....The approval by China’s National Medical Products Administration (NMPA) is based on the results of the DESTINY-Breast04 Phase III trial...

Daiichi Sankyo (TSE: 4568) today announced that ENHERTU® (trastuzumab deruxtecan) has been approved in Japan for the treatment of adult patients with HER2 low (IHC 1+ or IHC 2+/ISH-) unresectable or recurrent breast cancer after prior chemotherapy….The approval by Japan’s Ministry of Health, Labour and Welfare (MHLW) is based on results of the DESTINY-Breast04 phase 3 trial first presented at the American Society of Clinical Oncology 2022 Annual Meeting...

Daiichi Sankyo (Switzerland) AG received approval from Swissmedic for ENHERTU® (trastuzumab-deruxtecan) for patients with HER2 low-metastatic breast cancer....The approval is based on the DESTINY Breast04 study and allows the use of trastuzumab deruxtecan in HER2-low-expressing (IHC 1+ or IHC 2+/ISH-) metastatic breast cancer.

Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) ENHERTU® (trastuzumab deruxtecan) has been approved in the European Union (EU) as monotherapy indicated for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.

Health Canada approved Enhertu™ (trastuzumab deruxtecan) for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy....Approval based on the DESTINY-Breast04 results which showed Enhertu reduced risk of disease progression or death by 50 per cent and increased overall survival by more than six months versus chemotherapy...

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of: adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

Results from the 32-mo median F/U for DESTINY-Breast04 confirms the sustained clinically meaningful improvement for T-DXd vs TPC previously demonstrated in HER2-low mBC, regardless of HR status. Similar to the primary analysis, the overall safety profile was generally manageable with longer duration of treatment exposure.

Daiichi Sankyo and AstraZeneca’s ENHERTU® (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer...The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast04 phase 3 trial...

T-DXd showed responses in 7/14 (50%) pts in this subgroup vs 0/8 with TPC; this subgroup also had prolonged median PFS with T-DXd vs TPC (Table 3)....T-DXd treatment for HER2-low mBC in the phase 3 study DESTINY-Breast04 showed consistent efficacy independent of disease burden, prior CDK4/6i treatment, or rapid progression status...These data continue to support the use of T-DXd as the new standard of care across subgroups of pts with HER2-low mBC.

Findings from the phase III DESTINY-Breast04 trial indicate that the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is effective for patients with inoperable/metastatic HER2-low breast cancer. T-DXd should be considered a new standard of care for these patients, who otherwise have limited options.

AstraZeneca and Daiichi Sankyo have received notification of acceptance of the supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-negative) breast cancer who have received a prior therapy in the metastatic setting. The application has been granted Priority Review....The sBLA is based on data from the DESTINY-Breast04 Phase III trial...

Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P=0.001)....In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy.

Positive topline results from the pivotal DESTINY-Breast04 phase 3 trial showed ENHERTU® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2 low unresectable and/or metastatic breast cancer...

...HER2-low expressing status...

...- Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-low expression (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH-])...

...Real World Time to Next Treatment (rwTTNT1) in Participants With HER2-low Expressing Unresectable and/or Metastatic Breast Cancer...

...Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay 2....

...- Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which...

Pts with centrally confirmed HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization−) mBC who were previously treated with 1 or 2 lines of chemotherapy were randomized (2:1) to T-DXd or TPC….In this exploratory analysis, IC responses favored T-DXd over TPC in pts with clinically stable and treated baseline BMs.

...we designed DAISY, a phase 2 trial that evaluated T-DXd efficacy in patients with mBC according to HER2 expression levels and explored treatment response and resistance through biomarker analyses of tumor samples at different timepoints....Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2 expression above the median.

As for the tumor response rate, the pooled ORR and DCR of all studies reached 57% (95% CI: 47%–67%) and 92% (95% CI: 89%–96%) respectively, and the pooled ORRs of the HER2-low expression group and the HER2-positive expression group were 46% (95% CI: 35%–56%) and 64% (95% CI: 54%–74%)....The present study suggests that DS-8201 is effective and safe in the treatment of ABC with low or positive HER2 expression...

First cases of TDXD use in HER2-low BC patients in 2 French hospitals show promising results with a 54.5% response rate at 3 months. TDXD is globally well tolerated with 13.6% of grade ≥ 3 AE reported.

Overall, ORR-IC in all pts was 50% (6 of 12 pts; 95% CI, 21.1-78.9) and CBR was 66.7% (8 of 12 pts; 95% CI, 34.9-90.1). Combining pts with measurable intracranial or extracranial disease from cohorts 2 and 4, ORR, CBR and median DoR were 41.7% (5 of 12 pts; 95% CI, 15.2–72.3), 50.0% (6 of 12 pts; 95% CI, 21.1–78.9), and 7.2 months (95% CI, 2.5-16.4), respectively….T-DXd showed a preliminary antitumor activity in pretreated HER2-low ABC pts with asymptomatic untreated or progressing BM after local treatment.

In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11. In the subset of patients with untreated or progressive BCBM at baseline the CNS ORR was 70% (7/10)....T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM.

T-DXD showed meaningful antitumor activity in patients with mBC and history of BMs at baseline. Efficacy in Her2-low mBC is promising and warrants further investigation.

This ongoing phase 1 study (NCT02564900) enrolls subjects (sbj) with HER2+ breast cancer (BC) post T-DM1, HER2+ gastric cancer (GC) post trastuzumab, HER2 low BC (IHC 1+ or 2+, ISH-), and other HER2-expressing solid tumors (IHC ≥1+)....DS-8201a shows antitumor activity in multiple tumor types with high ORR and durable responses in heavily pretreated sbj.

The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months...The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer.