Enhertu, an antibody drug conjugate, being collectively developed by Daiichi Sankyo and AstraZeneca, has demonstrated a statistically important and clinically significant enchancment in general survival.
Up to date outcomes from DESTINY-Breast03 part 3 trial confirmed Enhertu (trastuzumab deruxtecan) was performing higher than trastuzumab emtansine (T-DM1) in sufferers with HER2 optimistic unresectable and/or metastatic breast most cancers beforehand handled with with trastuzumab and a taxane.
In the important thing secondary endpoint evaluation of general survival in DESTINY-Breast03, Enhertu demonstrated a 36% discount in danger of loss of life versus T-DM1. In each therapy arms, median general survival was not but reached after a median length of follow-up of 28.4 months for Enhertu and 26.5 months for T-DM1.
Within the Enhertu arm, an estimated 77.4% of sufferers have been alive at two years in comparison with 69.9% of sufferers handled with T-DM1. The noticed survival profit was constant throughout all analyzed subgroups. These included sufferers with or with out baseline mind metastases, with or with out baseline visceral illness. Moreover, those that have been hormone receptor (HR) optimistic or HR adverse and sufferers no matter prior pertuzumab or strains of systemic remedy have been additionally included.
Enhertu demonstrates discount in danger of loss of life
Sara Hurvitz, medical oncologist, mentioned: “The principle targets of remedy for superior breast most cancers are to regulate the illness and enhance survival, and it’s subsequently essential to proceed to enhance upon present therapy choices, significantly within the metastatic setting.
“For sufferers with HER2 optimistic breast most cancers who expertise illness development following preliminary therapy within the metastatic setting, Enhertu has proven important enchancment in survival in comparison with T-DM1, additional confirming this medication as the brand new customary of care.”
With the extra follow-up in DESTINY-Breast03, Enhertu additionally continued to show a clinically significant enchancment in progression-free survival (PFS) with a 22-month enchancment in median PFS over T-DM1, reaffirming the statistically important discovering on the earlier interim evaluation.
The up to date exploratory evaluation was not examined for statistical significance and never powered to indicate variations between therapy arms. The median PFS for sufferers within the Enhertu arm was 28.8 months in comparison with 6.8 months for T-DM1 as assessed by blinded unbiased central evaluate (BICR).
No new security considerations
Confirmed goal response price (ORR) was 78.5% within the Enhertu arm with 21.1% of sufferers demonstrating a whole response (CR) versus an ORR of 35.0% within the T-DM1 arm the place 9.5% of sufferers achieved a CR. The median length of response (DoR) was 36.6 months within the Enhertu arm and 23.8 months within the T-DM1 arm.
The protection profile noticed with Enhertu in DESTINY-Breast03 was in step with earlier scientific trials with no new security considerations recognized. Grade 3 or larger treatment-related therapy emergent antagonistic occasions (TEAEs) occurred in 47.1% of sufferers receiving Enhertu.
The commonest grade 3 or larger treatment-related TEAEs within the Enhertu arm have been decreased neutrophil rely (16.0%), anemia (9.3%), decreased platelet rely (7.8%), nausea (7.0%), decreased white blood cell rely (6.2%) and fatigue (5.8%).
Within the Enhertu arm, 15.2% of sufferers (n=39) skilled interstitial lung illness (ILD) or pneumonitis associated to therapy as decided by an unbiased adjudication committee. Nearly all of ILD or pneumonitis occasions have been low grade (grade 1 or grade 2) with two grade 3 occasions and no grade 4 or grade 5 occasions noticed in sufferers handled with Enhertu.
Additional validating the function of Enhertu
Ken Takeshita, world head, analysis and improvement, Daiichi Sankyo, mentioned: “The general survival advantages proven in each the DESTINY-Breast03 and DESTINY-Breast02 trials additional validate the function of Enhertu in probably extending the lives of sufferers with beforehand handled HER2 optimistic breast most cancers.
“Moreover, median progression-free survival was 4 instances longer with one in 5 sufferers exhibiting no detectable indicators of illness when handled with Enhertu in comparison with T-DM1 in DESTINY-Breast03, which is especially spectacular within the metastatic setting of HER2 optimistic breast most cancers.”
All sufferers in DESTINY-Breast03 acquired at the very least one prior most cancers remedy, together with trastuzumab or pertuzumab. Within the Enhertu arm, 41.4% of sufferers had acquired one prior line of remedy within the metastatic setting. At baseline, 16.5% of sufferers within the Enhertu arm and 14.8% of sufferers within the T-DM1 arm had a historical past of mind metastases. As of information cut-off on July 25, 2022, 75 sufferers remained on therapy with Enhertu and 18 sufferers on T-DM1.
Sufferers have extra disease-free time
Susan Galbraith, govt vice chairman, oncology analysis and improvement at AstraZeneca, mentioned: “The up to date outcomes for DESTINY-Breast03 exhibiting that Enhertu extends sufferers’ lives and in addition delays development by practically two years reinforces our perception that this medication has the potential to set a brand new customary of take care of sufferers with HER2 optimistic metastatic breast most cancers handled within the second-line setting.
“Complemented by DESTINY-Breast02, we now have two part 3 trials in HER2 optimistic metastatic breast most cancers exhibiting sufferers in these trials have extra disease-free time and dwell longer after they obtain Enhertu versus the earlier customary of care.”