Dr. Esserman on the I-SPY2 Trial in Breast Cancer

Laura J. Esserman, MD, MBA, discusses the rationale and design for the phase 2 I-SPY2 trial.

Laura J. Esserman, MD, MBA, Alfred A. de Lorimier Endowed Chair in General Surgery, professor, Departments of Surgery and Radiology, affiliate faculty, Institute for Health Policy Studies, University of California San Francisco (UCSF); director, UCSF Breast Care Center; co-leader, Breast Oncology Program, Helen Diller Family Comprehensive Cancer Center, discusses the rationale and design for the phase 2 I-SPY2 trial (NCT01042379).

I-SPY2 is a platform trial investigating the efficacy of combining several novel agents with standard chemotherapy in patients with breast cancer, with the goal of identifying optimal treatment strategies for different subsets based on molecular characteristics. This trial uses pathologic complete response as an early surrogate efficacy end point.

The aim of I-SPY2 is to determine therapies and treatment sequencing that will provide better outcomes to patients with breast cancer, such as those that are more effective and less toxic, Esserman says. This ongoing trial allows the opportunity to continually add new agents for investigation through 3 blocks of treatment categories—Blocks A, B, and C, Esserman explains.

Block A consists of the experimental regimens ARX788 with or without cemiplimab-rwlc (Libtayo), VSV-IFNβ-NIS plus cemiplimab, and datopotamab deruxtecan (DS-1062a) with or without durvalumab (Imfinzi). If patients are predicted to achieve CR with these agents, they’ll proceed to surgery, Esserman says. If they do not achieve a CR at 6 weeks, they will be assigned to Block B and receive the best available standard chemotherapy for their response predictive subtype, Esserman says. If patients have persistent disease after Block B, they will receive doxorubicin plus cyclophosphamide in Block C and proceed to surgery if they are predicted to have CR with this combination.

This trial uses MRI, functional tumor volume, and biopsy to predict which patients will have CRs to each block of therapy, Esserman adds. I-SPY2 follows standards that help investigators decide whether a patient will likely achieve a sufficient response based on their tumor type, Esserman says. This trial required all patients to have a biopsy at enrollment, allowing for molecular profiling that has helped to recategorize the breast cancer tumor types, Esserman explains.

For example, high-risk, hormone receptor–positive disease is heterogenous, as some tumors in this category have an immune phenotype that responds to treatment like a basal cancer would; others are not as responsive to the same treatments, Esserman notes. This trial has created a framework for assigning patients to the optimal therapies for their disease type, which will advance the breast cancer treatment landscape as this research evolves, Esserman concludes.

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