Dr Gluz on Ongoing Evaluations of De-Escalated Neoadjuvant Therapy in HR+/HER2+ Breast Cancer

"There are several ongoing trials worldwide [in patients with HR-positive, HER2-positive early breast cancer]…and our group is performing the WSG-ADAPT-HER2-IV trial to compare 12 weeks of…paclitaxel plus double anti-HER2 blockade vs antibody-drug conjugates like trastuzumab deruxtecan given for 12 weeks. We have to wait for results [from these studies] to figure out the best treatment for our patients."

Oleg Gluz, MD, chief physician of the West German Study Group at the Breast Center Niederrhein, discussed the continued investigation of de-escalated chemotherapy plus anti-HER2 blockade doublets for patients with hormone receptor (HR)–positive, HER2-positive early breast cancer.

At the 2024 ESMO Congress, findings from the phase 2 WSG-TP-II trial (NCT03272477) highlighted the potential of de-escalated therapeutic approaches for patients with stage I to III HR-positive, HER2-positive breast cancer. The trial evaluated the efficacy and tolerability of 2 neoadjuvant regimens administered over 12 weeks: endocrine therapy combined with trastuzumab (Herceptin) and pertuzumab (Perjeta), and a chemotherapy-based regimen of paclitaxel plus trastuzumab and pertuzumab. Both regimens showed high clinical activity and were well tolerated, supporting further exploration of de-escalation strategies in this disease subtype.

Multiple ongoing trials are continuing to investigate optimal de-escalated treatment approaches in this setting, Gluz stated. In the United States, the phase 2 CompassHER2-pCR (NCT04266249) and phase 3 CompassHER2 RD trials (NCT04457596) are evaluating the effects of 12-week chemotherapy-based regimens in broader patient populations, he detailed. Meanwhile, the phase 2 PHERGAIN-II trial (NCT04733118) is being conducted in Europe and is assessing a chemotherapy-free approach using pertuzumab, trastuzumab, and endocrine therapy in patients with small tumors, Gluz shared.

To build on this emerging evidence, the WSG collaborative group is conducting the phase 2 WSG-ADAPT-HER2-IV trial (NCT05704829), which directly compares 12 weeks of paclitaxel plus dual HER2 blockade with 12 weeks of the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu), Gluz continued. The goal of this trial is to determine whether newer targeted therapies may serve as alternatives to chemotherapy in the neoadjuvant setting, he explained. Collectively, these trials aim to refine treatment strategies by balancing efficacy with toxicity, with the ultimate objective of identifying the most appropriate and least burdensome therapies for patients with early-stage HR-positive, HER2-positive breast cancer, Gluz concluded.