In a significant development for metastatic breast cancer treatment, researchers at Dana-Farber Cancer Institute are pursuing two innovative clinical trials that could revolutionize the treatment approach for HER2-positive metastatic breast cancer patients, potentially offering paths to long-term remission or cure.
About 20% of all breast cancer cases are HER2-positive, and currently, approximately 16% of patients with HER2-positive metastatic breast cancer achieve undetectable cancer levels and survive for many years after treatment. These encouraging statistics have prompted researchers to explore more aggressive and potentially curative approaches.
Challenging Traditional Maintenance Therapy
The STOP-HER2 trial, led by Dr. Heather Parsons, challenges the conventional wisdom of indefinite maintenance therapy. The study focuses on exceptional responders – patients whose cancer hasn't progressed after three years of maintenance therapy with trastuzumab and pertuzumab.
"People are sometimes hesitant to use the word cure," says Dr. Parsons. "But we want to know if we can help people control their cancer and live for a long time without being on constant therapy."
The trial incorporates innovative monitoring approaches, including circulating tumor DNA (ctDNA) testing alongside traditional CT scans, potentially offering more precise ways to track disease status. Patients are followed for ten years to ensure the safety and efficacy of treatment discontinuation.
SAPPHO Trial: An Intensive Approach to Prevention
The SAPPHO trial represents an even more ambitious approach to treating newly diagnosed HER2-positive metastatic breast cancer. Instead of the traditional sequential treatment approach that waits for cancer progression before introducing new therapies, SAPPHO implements an intensive, back-to-back regimen of multiple HER2-targeted therapies.
The treatment protocol includes:
- Standard chemotherapy plus trastuzumab and pertuzumab
- Trastuzumab deruxtecan (T-DXd)
- Tucatinib combined with T-DM1
- Maintenance therapy with trastuzumab, pertuzumab, and tucatinib
"These medicines are hitting the same target, but not in the same way, which we think can address some heterogeneity," explains Dr. Parsons. The strategy aims to prevent cancer cells from developing resistance by maintaining continuous pressure through different mechanisms of action.
Real-World Impact
The potential impact of these trials is illustrated by patients like Yvonne Fantaci, who was diagnosed with metastatic breast cancer at age 60. After treatment, her 11 lesions shrank to virtually undetectable levels, and she has maintained this response for seven years.
"I am just so grateful," says Fantaci, who participated in the STOP-HER2 trial. "There are some days where it's an overwhelming sense of gratitude that I am here. Ten or 15 years ago, it might have been a different story."
Dr. Erica Mayer, director of clinical research in Dana-Farber's breast oncology program, notes the remarkable progress in HER2-positive breast cancer treatment: "The use of these and other more recently developed HER2-directed therapies have made a dramatic impact on our ability to prolong survival for patients with advanced disease and to cure patients with early-stage disease."
While the researchers maintain cautious optimism, their goal is ambitious – to significantly increase the percentage of patients who achieve long-term progression-free survival beyond the current 16% rate. The SAPPHO trial aims for at least 24% of patients to become exceptional responders, with hopes for even better outcomes.
