Genentech, a member of the Roche Group, along with the Breast International Group (BIG), Institut Jules Bordet Clinical Trials Support Unit, and Frontier Science Foundation, has announced significant final overall survival results from the Phase III APHINITY study after ten years of follow-up.
The landmark data, to be presented as a late-breaking abstract at the 2025 European Society for Medical Oncology (ESMO) Breast Cancer Congress, shows that adding Perjeta (pertuzumab) to standard Herceptin (trastuzumab) and chemotherapy reduced the risk of death by 17% in patients with HER2-positive early-stage breast cancer.
Significant Survival Benefit Demonstrated
After a decade of follow-up, the results revealed that 91.6% of patients treated with the Perjeta-based regimen were alive at ten years compared to 89.8% of those who received Herceptin, chemotherapy, and placebo (hazard ratio [HR]=0.83, 95% CI: 0.69-1.00, p-value=0.044).
The benefit was particularly pronounced in the pre-specified subgroup of patients with lymph node-positive disease, who experienced a 21% reduction in the risk of death (HR=0.79, 95% CI: 0.64-0.97). No benefit was observed in the node-negative subgroup.
"After ten years, the APHINITY trial clearly shows a statistically significant and clinically meaningful improvement of the overall survival," said Prof. Sibylle Loibl, APHINITY Study Chair and Chair of the German Breast Group. "Adding Perjeta to a standard adjuvant treatment is most beneficial for people with HER2-positive breast cancer with lymph node-positive disease who are at high risk of recurrence."
Reinforcing Earlier Findings
The latest analysis also confirmed that the previously reported invasive disease-free survival (the primary endpoint) benefit was maintained (HR=0.79, 95% CI: 0.68-0.92), strengthening results from earlier analyses.
"Early treatment of breast cancer can provide substantial patient benefit and also increases the chance for cure. For people with early-stage HER2-positive disease, the APHINITY results validate the sustained benefits of the Perjeta-based regimen," said Levi Garraway, M.D., Ph.D., Genentech's Chief Medical Officer and Head of Global Product Development. "These long-term data reinforce the regimen's value as a well-established standard-of-care treatment in the curative setting."
The safety profile, including cardiac safety, remained consistent with previous studies, with no new or unexpected safety signals identified.
About the APHINITY Study
APHINITY is a global, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy, compared with Herceptin and chemotherapy alone, as post-surgery (adjuvant) treatment in 4,804 people with operable HER2-positive early-stage breast cancer.
The primary endpoint is invasive disease-free survival, defined as the time a patient lives without recurrence of invasive breast cancer or death from any cause after post-surgery treatment. Secondary endpoints include cardiac and overall safety, overall survival, and health-related quality of life.
Liz Frank, an independent research advocate, highlighted the importance of the international collaborations in APHINITY: "Scientists and clinicians are working together with the broader goal of improving our understanding of HER2-positive breast cancer, improving the quality of life for people living with the disease and ultimately, helping them to live longer with no disease occurring."
Implications for Clinical Practice
The collaborative efforts of Genentech, BIG, and study partners enabled the initiation of pivotal trials such as APHINITY and HERA. These studies have led to Herceptin and Perjeta becoming standards of care and have helped improve outcomes for people with early-stage HER2-positive breast cancer.
HER2-positive breast cancer affects approximately 15-20% of people with breast cancer and was once seen as an aggressive type of the disease. However, the development of targeted therapies has transformed survival outcomes, making long-term survival a possibility for many patients.
The Perjeta-based regimen is currently approved in more than 120 countries/regions for the treatment of both early-stage and metastatic HER2-positive breast cancer. Phesgo, a subcutaneous fixed-dose combination of Perjeta and Herceptin, is also available, providing faster and more flexible administration in approximately eight minutes, compared to hours with standard intravenous administration.
These long-term results from APHINITY further solidify the role of dual HER2 blockade with Perjeta and Herceptin in the treatment paradigm for early-stage HER2-positive breast cancer, particularly for those with lymph node-positive disease who face a higher risk of recurrence.
