Enhertu (trastuzumab deruxtecan) and Trodelvy (sacituzumab govitecan), the two breast cancer therapies based on the next-generation antibody-drug conjugates (ADC), will likely take the lead in the cancer’s innovative treatment across the board.
The first-generation ADC developed by Roche, Kadcyla (trastuzumab emtansine), stood at curing epithelial cell growth factor receptor-2 positive (HER2+) breast cancer.
However, the two follow-up treatments seem to have overcome the stage.
Gilead said Tuesday that Trodelvy would receive a quick review from the U.S. Food and Drug Administration for treating metastatic hormone receptor-positive (HR+) breast cancer.
More precisely, it targets adult patients with non-abstract local progressive or metastatic HR+/HER2- breast cancer who have previously received at least two systemic treatments. Gilead expects the U.S. FDA to approve it next February.
Gilead's application for approval has accelerated after Trodelvy proved improvement in overall survival (OS), following progression-free survival (PFS) in a recent phase 3 clinical trial, TROPiCS-02 study.
In the TROPiCS-02 study, Trodelvy lowered the disease progression-and- death risk by 34 percent and overall death risk by 21 percent compared to existing chemotherapies (medical professionals choose among capecitabine, vinorelbine, gemcitabine, and eribulin) in patients who have received one or more endocrine treatments, taksene, CDK4/6 inhibitors and two to four rounds of chemotherapy.
The median duration of progression-free survival (mPFS) was 5.5 months in the Trodelvy treatment group and four months in the chemotherapy group. The total survival period (mOS) median value was 14.4 months to 11.2 months.
Trodelvy is the first and only ADC approved in the U.S. for metastatic triple-negative breast cancer (TNBC) treatment. If the FDA approves HR+/HER2- breast cancer treatment indication, Trodelvy will move beyond TNBC, which accounts for only 15 percent of all breast cancer patients, and affect the HR+/HER2- domain, which accounts for about 70 percent of the total patients.
Trodelvy is also expected to compete with Enhertu, an archrival in the field of breast cancer treatment.
Enhertu is also the next-generation ADC attracting the most attention worldwide. It easily defeated the first-generation formulation Kadcyla in head-to-head research. Enhertu has become the standard therapy for the secondary treatment of metastatic patients.
In the phase 3 clinical trial of the DESTINY-Breast03 study, Enhertu reduced the risk of disease progression and death by 72 percent compared to Kadcyla. It also nearly doubled the response rate (79.7 percent vs. 34.2 percent).
Enhertu's territorial expansion did not stop there. In HER2 low-expression patients, which account for more than half of breast cancer patients, it marked a milestone in the history of breast cancer treatment by lowering the risk of disease progression and death risks by 50 percent compared to conventional chemotherapies.
DESTINY-Breast04 study, a phase 3 clinical trial that produced such results, was selected as the plenary theme at the annual conference of the American Society for Clinical Oncology (ASCO 2022) in June. The FDA also broke a record by approving expanding Enhertu’s indication less than two weeks after it applied based on such data.
Enhertu also expanded from the HER2+ area accounting for only 15 percent of the total to HER2, which takes up 55 percent of patients, affecting metastatic breast cancer patients, who account for 70 percent.
Moreover, Enhertu has the potential to expand from TNBC to HR+/HER2- area, where Trodelvy has proved its effectiveness this time around, emerging as the most promising option to treat breast cancer.