Enhertu confirmed improved progression-free survival in contrast with doctor’s alternative of remedy in sure sufferers with metastatic breast most cancers.
Sufferers with hormone receptor (HR)-positive, HER2-low/-ultralow metastatic breast most cancers skilled enhancements to progression-free survival (PFS) from remedy with Enhertu (fam-trastuzumab deruxtecan-nxki) compared with remedy of doctor’s alternative (TPC), regardless of the time to development (TTP) on frontline endocrine remedy with CDK4/6 inhibition and the kind of endocrine resistance, examine outcomes have proven.
Information from the section 3 DESTINY-Breast06 trial had been introduced in the course of the 2024 San Antonio Breast Most cancers Symposium.
Within the inhabitants of sufferers who had a TTP of lower than six months, the median PFS was 14 months with Enhertu versus 6.5 months with TPC. Sufferers with a TTP between 6 and 12 months had a median PFS of 13.2 months with Enhertu versus 6.9 months with TPC. Sufferers who went greater than 12 months earlier than progressing on frontline remedy skilled a median PFS of 12.9 months with Enhertu versus 8.2 months with TPC.
Glossary
Development-free survival (PFS): the time a affected person lives with out their illness spreading or worsening.
Goal response price (ORR): sufferers who responded partially or utterly to remedy.
Length of response (DOR): how lengthy a affected person responds to remedy.
Time to second development: the time till a second illness development.
Furthermore, the median PFS was 12.4 months with Enhertu versus 6.6 months with TPC in sufferers with major endocrine resistance. Sufferers with secondary endocrine resistance achieved a median PFS of 13.2 months with Enhertu versus 9.5 months with TPC.
“[Enhertu] demonstrated a clinically significant efficacy profit versus TPC no matter time to development on frontline endocrine remedy plus CDK4/6 inhibition, in addition to efficacy no matter illness burden,” Dr. Aditya Bardia, lead examine creator and professor within the Division of Drugs, Division of Hematology/Oncology at UCLA Well being’s Jonsson Complete Most cancers Middle in Los Angeles, California, stated in a presentation of the information.
The multi-center, open-label DESTINY-Breast06 trial enrolled sufferers with hormone receptor-positive metastatic breast most cancers with HER2-low or HER2-ultralow expression. Sufferers couldn’t have acquired prior chemotherapy and should have had no less than two prior strains of endocrine remedy with or with out focused remedy for metastatic illness or acquired one line of remedy for metastatic illness and developed development inside six months of beginning frontline endocrine remedy with a CDK4/6 inhibitor or developed recurrence inside 24 months of beginning adjuvant endocrine remedy.
Sufferers had been randomly assigned evenly to five.4 milligrams per kilogram (mg/kg) of Enhertu each 3 weeks (436 sufferers) or TPC (430 sufferers), which consisted of Xeloda (capecitabine; 59.8%), Abraxane (nab-paclitaxel; 24.4%) or paclitaxel (15.8%).
The examine had beforehand met its major finish level, demonstrating an enchancment in PFS within the HER2-low inhabitants. A key secondary finish level of PFS within the HER2-low/-ultralow inhabitants was additionally met.
“The targets of this evaluation had been to research the good thing about Enhertu in sufferers with completely different responses to endocrine remedy, assess the efficacy of subsequent therapies publish development on Enhertu/TPC and perceive the good thing about Enhertu in sufferers with various illness burdens,” Bardia stated.
Investigators additionally discovered that Enhertu improved the target response price (ORR) and length of response (DOR) versus TPC throughout all TTP subgroups and in sufferers with major and secondary endocrine resistance. The confirmed ORRs with Enhertu and TPC, respectively, had been 67.7% and 25.4% in sufferers with a TTP of lower than six months; 60% and 28.8% in sufferers with a TTP between six and 12 months; and 59.5% and 33.1% in sufferers with a TTP better than 12 months.
The confirmed ORRs had been 57.8% and 25.7% with Enhertu and TPC, respectively, in sufferers with major endocrine resistance; and 57.1% and 34.0%, respectively, in these with secondary endocrine resistance.
The median DOR with Enhertu and TPC, respectively, in sufferers with a TTP of lower than six months, between six and 12 months, and better than 12 months had been as follows: 11.1 months versus 7.3 months; 13.7 months versus 11.5 months and 15.7 months versus 11.1 months. The median DOR was 11.1 months with Enhertu versus 7.3 months with TPC in sufferers with major endocrine resistance and 15.4 months versus 10.1 months in these with secondary endocrine resistance.
Time to second development (PFS2), which served as a secondary finish level of the trial, was additionally introduced within the intention-to-treat inhabitants (866 sufferers). Findings confirmed that the median PFS2 was 20.3 months with Enhertu versus 14.7 months with TPC. Bardia said that PFS2 was clinically significant in favor of Enhertu throughout all TTP subgroups. Sufferers with a TTP of lower than six months had a median PFS2 of 18.9 months with Enhertu versus 15.2 months with TPC. Sufferers with a TTP between six and 12 months had a median PFS2 of 17.1 months with Enhertu versus 13.7 months with TPC. Sufferers with a TTP better than 12 months had a median PFS2 of 20 months with Enhertu versus 14.3 months with TPC.
“PFS profit with [Enhertu] was [also] noticed no matter illness burden, with notable efficacy in sufferers with decrease illness burden,” Bardia stated. In sufferers with lower than three native or metastatic websites at baseline the median PFS was 15.3 months with Enhertu versus 8.4 months with TPC. Amongst sufferers with no less than three native or metastatic websites at baseline the median PFS was 11.4 months with Enhertu versus 7.2 months with TPC.
Enhertu additionally improved PFS versus TPC in sufferers with and with out liver metastases, a baseline tumor dimension better and decrease than the median and people with and with out visceral illness.
With respect to security, Bardia defined that the security profiles for Enhertu and TPC within the TTP and illness burden subgroups had been according to the general inhabitants.
Reference
“Efficacy and security of trastuzumab deruxtecan (T-DXd) vs doctor’s alternative of chemotherapy (TPC) by tempo of illness development on prior endocrine-based remedy: further evaluation from DESTINY-Breast06” by Dr. Aditya Bardia et al., introduced at: San Antonio Breast Most cancers Convention; December 10-13, 2024; San Antonio, Texas.
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