Balancing Breast Cancer Breakthroughs With Clinical, Financial, and Diagnostic Barriers: Michael Hassett, MD, MPH

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Cancer treatment is a highly dynamic field where research continually evolves, leading to new therapeutic approaches. Historically, treatments proven effective in later lines of therapy (second, third, and fourth) are often moved to earlier stages of care. A significant development in this area is the comparison of trastuzumab deruxtecan (T-DXd; Enhertu; Daiichi Sankyo/AstraZeneca) to the current standard of care for first-line metastatic HER2-positive breast cancer, which traditionally involves a taxane, trastuzumab, and pertuzumab, according to Michael Hassett, MD, MPH, chief quality officer at Dana-Farber Cancer Institute in Boston. Early findings suggest improvements in progression-free survival with T-DXd.

Despite its potential, incorporating new treatments like T-DXd into a first-line setting faces several barriers. One key challenge is balancing the observed benefit with potential adverse effects. The “old paradigm” for treatment, Hasset explains, often involved a 6-cycle induction phase followed by long-term maintenance where adverse effects were very low, which was considered patient friendly. However, newer regimens may require patients to remain on treatment without a distinct induction or maintenance phase, potentially leading to more consistent adverse effects vs a maintenance trastuzumab/pertuzumab (Herceptin/Perjeta, both Genentech), or HP, phase. This is particularly relevant for patients with relatively low-volume disease who want to minimize the impact of treatment on their daily lives.

Another significant barrier is the cost of care, especially for prescription medicines, due to differences in pharmacy benefit compared with infusional therapy coverage.

Another critical barrier revolves around pathology and testing, Hassett notes. Ensuring that the right patients receive these treatments is complex, particularly as T-DXd is now being used beyond classic HER2-positive (IHC 3+) cancers to include those that are 2+, 1+, and less than 1+, or ultra-low disease. Pathologists are adapting to analyze new specimens for classifications like HER2 ultra-low, but because this doesn't apply to older specimens, when treatment changes, it might be necessary to reanalyze old tissue or perform new biopsies to determine eligibility for T-DXd, which can be a constraint, especially if the original tissue is unavailable.

To overcome these challenges, efforts are underway: pathologists are pivoting to new analysis methods for new specimens, resource officers help address financial difficulties, and clinicians make decisions at the point of care to balance the burden of cancer with the acceptance of potential adverse effects, especially when a higher response rate is needed early on, Hassett explains.