APHINITY Trial Shows Perjeta-Based Regimen Improves 10-Year Overall Survival in HER2-Positive Early Breast Cancer
Final overall survival results from the Phase III APHINITY trial show a 17% reduction in the risk of death at 10 years for patients with HER2-positive early-stage breast cancer treated with a Perjeta-based adjuvant regimen.
Credit: David A Litman | stock.adobe.com
Long-term overall survival (OS) data from the Phase III APHINITY trial (NCT01358877) show a Perjeta-based adjuvant regimen produced a statistically significant reduction in the risk of death at 10 years in patients with HER2-positive early-stage breast cancer.1,2 Results from the trial, which compared the combination of Perjeta plus Herceptin (trastuzumab) and chemotherapy administered for one year post-surgery vs. the combination of Herceptin, chemotherapy, and placebo, were presented at the 2025 European Society for Medical Oncology Breast Cancer Congress.
"After 10 years, the APHINITY trial clearly shows a statistically significant and clinically meaningful improvement of the overall survival," APHINITY study chair Sibylle Loibl, chair of the German Breast Group (GBG) and CEO of the GBG Forschungs GmbH, said in a press release. “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.”1
Perjeta is a targeted HER2 inhibitor that attaches to HER2 receptors on the surface of breast cancer cells and stops them from receiving growth signals. Perjeta has also been found to inhibit breast cancer development by alerting the immune system to attack and destroy cancer cells that the drug attached to.3
The drug has been approved by the FDA in combination with Herceptin and docetaxel to treat patients with HER2-positive metastatic breast cancer who were not previously administered anti-HER2 therapy or chemotherapy for metastatic disease; and in combination with Herceptin and docetaxel for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen for early breast cancer.
Trial Design
The global, randomized, double-blind, placebo-controlled, two-arm APHINITY trial analyzed the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin plus chemotherapy in the adjuvant treatment in 4,804 patients with operable HER2-positive early-stage breast cancer. The trial’s primary endpoint is invasive disease-free survival (iDFS) defined as time without recurrence of invasive breast cancer or death from any cause after adjuvant treatment. The trial’s secondary endpoints included cardiac and overall safety, OS, and health-related quality of life.
Results show that at 10 years, patients administered the Perjeta-based regimen had a 17% lower risk of death compared to the placebo combination cohort. A total of 91.6% of patients administered the Perjeta regimen were alive at ten years compared to 89.8% in the placebo cohort (hazard ratio [HR]=0.83, 95% CI: 0.69-1.00, p-value=0.044).
The Perjeta combination was also found to lower the risk of death by 21% in a prespecified subgroup of patients with lymph node-positive disease (HR=0.79, 95% CI: 0.64-0.97). The trial previously achieved the primary iDFS endpoint, which was maintained across the earlier APHINITY analyses (HR=0.79, 95% CI: 0.68-0.92); however, there were no observed benefits in the node-negative patient subgroup.
In terms of safety, the profile of the Perjeta regimen was consistent with prior findings and no new safety signals were reported.
“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,” Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development, said in the release. “These long-term data reinforce the regimen’s value as a well-established standard-of-care treatment in the curative setting.”1
References
1. Ten-year APHINITY data show Roche’s Perjeta-based regimen reduced the risk of death by 17% in people with HER2-positive early-stage breast cancer. News release. Roche. May 12, 2025. Accessed May 13, 2025. https://www.roche.com/media/releases/med-cor-2025-05-13
2. A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer (APHINITY). ClinicalTrials.gov. Updated January 13, 2025. Accessed May 13, 2025. https://clinicaltrials.gov/study/NCT01358877#study-overview
3. Perjeta. Webpage. BreastCancer.org. Updated March 4, 2025. Accessed May 13, 2025. https://www.breastcancer.org/treatment/targeted-therapy/perjeta
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