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

• Long term follow-up in this curative setting demonstrated clinically meaningful survival benefit when adding adjuvant Perjeta® (pertuzumab) to Herceptin® (trastuzumab) and chemotherapy¹
• 21% reduction in the risk of death was seen in the pre-specified subgroup of people with lymph node-positive disease¹
• Data to be presented as a late-breaking abstract at the 2025 European Society for Medical Oncology (ESMO) Breast Cancer Congress

Basel, 13 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY), the Breast International Group (BIG), Institut Jules Bordet Clinical Trials Support Unit and Frontier Science Foundation, announced today statistically significant final overall survival (OS) results from the phase III APHINITY study in people with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer.¹ After ten years, the risk of death was reduced by 17% for people treated with Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy (the Perjeta-based regimen) for a year as post-surgery (adjuvant) treatment, compared with individuals who received Herceptin, chemotherapy, and placebo.¹

“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., Roche’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.”

"After 10 years, the APHINITY trial clearly shows a statistically significant and clinically meaningful improvement of the overall survival," said Prof. Sibylle Loibl, APHINITY Study Chair, Chair of the German Breast Group (GBG) and the Chief Executive Officer of the GBG Forschungs GmbH. “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.”

After ten years, results show:

• 91.6% of people treated with the Perjeta-based regimen were alive at ten years versus 89.8% of those treated with Herceptin, chemotherapy, and placebo (hazard ratio [HR]=0.83, 95% CI: 0.69-1.00, p-value=0.044).¹
• A 21% reduction in the risk of death was seen in the prespecified subgroup of people with lymph node-positive disease (HR=0.79, 95% CI: 0.64-0.97).¹
• The previously reported invasive disease-free survival (primary endpoint) benefit was maintained (HR=0.79, 95% CI: 0.68-0.92), strengthening results from earlier APHINITY analyses.^1,2 No benefit was seen in the node negative subgroup.¹
• The safety profile, including cardiac safety, was consistent with previous studies and no new or unexpected safety signals were identified.^1,2

Full results will be presented as a late-breaking abstract on Thursday, 15 May at the 2025 European Society for Medical Oncology Breast Cancer Congress.

“The international collaborations in APHINITY have facilitated important insights about HER2-positive breast cancer and are continuing to yield promising findings,” said Liz Frank, Independent Research Advocate. “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.”

The collaborative efforts of Roche, BIG, and study partners enabled the initiation of pivotal trials such as APHINITY and HERA. These studies led to Herceptin and Perjeta becoming standards of care and helped improve outcomes for people with early-stage HER2-positive breast cancer.³

About the APHINITY study
APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is a global, phase III, randomised, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta® (pertuzumab) plus Herceptin® (trastuzumab) and chemotherapy, compared with Herceptin and chemotherapy, as post-surgery (adjuvant) treatment in 4,804 people with operable human epidermal growth factor receptor 2-positive early-stage breast cancer.⁴

The primary endpoint is invasive disease-free survival, which in this study is defined as the time a patient lives without recurrence of invasive breast cancer (when the cancer returns locally or spreads into the surrounding breast tissue and/or beyond) or death from any cause after post-surgery treatment.⁴ Secondary endpoints include cardiac and overall safety, overall survival and health-related quality of life.⁴

About the Perjeta-based regimen (intravenous (IV) Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy)
The Perjeta-based regimen is approved in more than 120 countries/regions for the treatment of both early-stage and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In the neoadjuvant (before surgery) early-stage breast cancer setting, the Perjeta-based regimen has been shown to almost double the rate of pathological complete response compared to Herceptin and chemotherapy.⁵ Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant (after surgery) early-stage breast cancer setting.⁶ In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.⁷ Phesgo® – a subcutaneous fixed-dose combination of Perjeta and Herceptin – is also approved in more than 120 countries/regions and provides faster and more flexible administration of Perjeta and Herceptin under the skin in approximately eight minutes, compared to hours with standard IV administration.^8,9 The European Medicines Agency’s Committee for Medicinal Products for Human Use recently recommended updating Phesgo’s label in the European Union to allow administration outside of a clinical setting (such as in a person’s home) by a healthcare professional, which can help to alleviate treatment burden and free up cancer care capacity in clinics.¹⁰

About Roche’s medicines for human epidermal growth factor receptor 2 (HER2)-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early-stage and advanced HER2-positive disease. HER2-positive breast cancer affects approximately 15-20% of people with breast cancer.¹¹

Survival outcomes for people with HER2-positive breast cancer, once seen as an aggressive type of the disease, have been transformed through the development of targeted therapies, including Roche molecules Herceptin® (trastuzumab), Perjeta® (pertuzumab), Kadcyla® (trastuzumab emtansine) and Phesgo® (pertuzumab, trastuzumab, and hyaluronidase subcutaneous).^12,13 Long-term survival is now a possibility for many people, which also contributes to societal and economic benefits.¹⁴

Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.

About Roche in breast cancer
Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.

About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045.

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1] Loibl S, et al. Adjuvant pertuzumab or placebo + trastuzumab + chemotherapy (P or Pla + T + CT) in patients (pts) with early HER2-positive operable breast cancer in APHINITY: Final analysis at 11.3 years’ median follow-up. Presented at: ESMO Breast Cancer; 2025 May 14-17; Munich, Germany. Abstract #LBA1.
[2] Loibl S, et al. VP6-2022: Adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years' follow-up. Annals of Oncology. 2022;33(9):986-987.
[3] National Comprehensive Cancer Network (NCCN). NCNN Guidelines Insights [Internet; cited 2025 May]. Available from: https://jnccn.org/view/journals/jnccn/22/5/article-p331.xml.
[4] Clinicaltrials.gov. 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) [Internet; cited May 2025]. Available from: https://clinicaltrials.gov/ct2/show/NCT01358877.
[5] Gianni L, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.
[6] Minckwitz G, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017;377(2):122-131.
[7] Swain M, et al. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2015;372(8):724-734.
[8] PHESGO pertuzumab/trastuzumab/hyaluronidase-zzxf. Recommended dosing and administration for PHESGO [Internet; cited 2025 May]. Available from: https://www.phesgo-hcp.com/dosing/dosing-administration.html.
[9] Perjeta pertuzumab. Early Breast Cancer Treatment. The infusion process [Internet; cited 2025 May]. Available from: https://www.perjeta.com/early-breast-cancer/iv-infusion.html.
[10] O’Shaughnessy J, et al. Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. Eur J Cancer. 2021;152:223-232.
[11] Ban M, et al. Early HER2-positive breast cancer: current treatment and novel approaches. Breast Care. 2020;15(6):560-569.
[12] Ligorio F, et al. Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications. Ther Adv Med Oncol. 2022;14(1):17588359221079123.
[13] Mendes D, et al. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer–a systematic review. Breast Cancer Research. 2015;17:140.
[14] WifOR Institute. The Value of Investing in Innovative Medicines: Socioeconomic Burden and Annual Social Impact of Roche Treatments for HER2+ Breast Cancer, Multiple Sclerosis and Retinal Disease [Internet; cited 2025 May]. Available from: https://www.wifor.com/en/download/the-value-of-investing-in-innovative-medicines-socioeconomic-burden-and-annual-social-impact-of-roche-treatments-for-her2-breast-cancer-multiple-sclerosis-and-retinal-disease/.

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