Mediamedic – SABCS 2024: Clinical Symposium on Dose Optimization and Regimen Design in Breast Oncology

Mediamedic shared on LinkedIn:

“SABCS2024 Rethinking Dosing: Clinical Symposium on Optimizing Regimens in Breast Oncology
At SABCS 2024, experts explored advancements in dose optimization for breast cancer therapies, shifting from maximum tolerated doses to individualized strategies for targeted treatments, redefining precision oncology practices.

The session was co-chaired by Dr. Mirat Shah, Clinical Lead of Project Optimus—a U.S. FDA Oncology Center of Excellence initiative to reform dose-selection paradigms—and Dr. Patricia LoRusso, Professor of Medicine at Yale School of Medicine, Director of Experimental Therapeutics, and Associate Director of Experimental Therapeutics at Yale Cancer Center.”

Dr. Mirat Shah opened the session by highlighting the limitations of MTD-dependent approaches, emphasizing that:

“Continued reliance on MTD methods may result in inadequate characterization of the dose and regimen of molecular targeted therapies before initiating registrational trials.”

She explained that suboptimal dose regimens could lead to higher toxicity without corresponding efficacy benefits, necessitating frequent dose reductions or even treatment discontinuation. These outcomes could prevent patients from achieving prolonged benefits from therapies and risk introducing persistent or irreversible toxicities that limit future treatment options.

Dr. Shah stressed the importance of a paradigm shift from MTD to dose optimization, which evaluates a broader range of factors, including pharmacokinetics, pharmacodynamics, safety, tolerability, efficacy, and dose-response relationships.

She noted, “Dose optimization aims to strike the best balance between therapeutic benefits and risks for patients. This approach is particularly relevant as multi-phase treatments—such as neoadjuvant and adjuvant therapies—become more prevalent. However, it’s not always clear which elements of a specific therapy are necessary or appropriate to maximize long-term outcomes.”

Patient Preferences in Dose Optimization

Dr. Shah emphasized that patient preferences are becoming increasingly significant in dose-selection decisions. Even toxicities below life-threatening levels may be intolerable for patients, leading them to decline otherwise effective treatments.

She explained:

“Patients have highlighted the importance of considering chronic, low-grade symptomatic toxicities, such as diarrhea, when making dosing decisions. For instance, Grade 2 diarrhea, characterized by four to six additional daily bowel movements compared to baseline, can profoundly impact quality of life if endured for months. Patient-reported outcomes are invaluable in understanding tolerability.”

Cross-Over Designs in Trials

Another critical topic discussed during the symposium was cross-over trial designs.

Dr. Shah noted that many patients prefer trial designs that allow those randomized to the standard treatment arm to access the investigational drug upon disease progression. However, she acknowledged that researchers often view these designs less favorably, as they can complicate the evaluation of long-term endpoints such as overall survival.

“Through this symposium, we aim to encourage patients and oncologists to advocate for dose optimization early in drug development and encourage clinical researchers to address dose and regimen optimization in trials supporting drug approval,” Dr. Shah concluded.

The session underscored the evolving priorities in breast oncology—focusing not only on maximizing efficacy but also on ensuring treatments align with patient needs, preferences, and overall quality of life.”