Phase III APHINITY Study: Adjuvant Pertuzumab/Trastuzumab/Chemotherapy Increased Invasive Disease–Free Survival in HER2-Positive Breast Cancer


Genentech, the Breast International Group, the Breast European Adjuvant Study Team, and the Frontier Science Foundation have announced positive results from the phase III APHINITY study. The study met its primary endpoint and showed that adjuvant treatment with the combination of pertuzumab (Perjeta), trastuzumab (Herceptin), and chemotherapy (the pertuzumab-based regimen) achieved a statistically significant reduction in the risk of recurrence of invasive disease or death (invasive disease–free survival) in patients with HER2-positive early breast cancer compared to trastuzumab and chemotherapy alone. The safety profile of the pertuzumab-based regimen was consistent with that seen in previous studies, and no new safety signals were identified. 

“These results from the positive APHINITY study represent an important addition to the body of data for [pertuzumab] in the treatment of people with HER2-positive early breast cancer,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Genentech. Full results from the APHINITY trial will be presented at an upcoming medical meeting in 2017.

Gunter von Minckwitz, MD, study coordinator from the Breast International Group and academic study partners, added, “APHINITY provides yet another example of the importance of industry-academic collaborations and their value in advancing cancer care for people affected by this challenging disease.”

HER2-Positive Breast Cancer Treatment

HER2-positive breast cancer affects approximately one in five people with breast cancer and is associated with a poor prognosis if left untreated. Despite advancements in the treatment of HER2-positive early breast cancer, up to one in three people treated with trastuzumab and chemotherapy may eventually see their cancer return. Treating breast cancer early, before it has metastasized, may improve the chance of preventing the disease from returning and potentially reaching an incurable stage.

In the U.S., the combination of pertuzumab, trastuzumab, and docetaxel chemotherapy is currently available under accelerated approval for neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer. This approval was based primarily on data from a phase II study showing that nearly 40% of people receiving the combination of pertuzumab, trastuzumab, and docetaxel chemotherapy had a pathologic complete response compared to almost 22% in the trastuzumab and docetaxel chemotherapy arm.


APHINITY (NCT01358877/BO25126/BIG 4-11) is an international, phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of pertuzumab plus trastuzumab and chemotherapy compared to trastuzumab and chemotherapy as an adjuvant therapy in 4,805 people with operable HER2-positive early breast cancer.

People enrolled in the study underwent surgery and were randomized to one of two arms (1:1) to receive either:

  • Six to eight cycles of chemotherapy (anthracycline-containing or non–anthracycline-containing regimen) with pertuzumab and trastuzumab, followed by pertuzumab and trastuzumab every 3 weeks for a total of 1 year of treatment.
  • Six to eight cycles of chemotherapy (anthracycline-containing or non–anthracycline-containing regimen) with placebo and trastuzumab, followed by placebo and trastuzumab every 3 weeks for a total of 1 year of treatment. 

Radiotherapy and/or endocrine therapy could be initiated at the end of adjuvant chemotherapy. The APHINITY study allowed for a range of standard chemotherapy regimens to be used and both lymph node–positive and lymph node–negative participants were eligible for enrollment. The primary efficacy endpoint of the APHINITY study is invasive disease–free survival. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival, and health-related quality of life.

About Pertuzumab and Trastuzumab

Pertuzumab is a monoclonal antibody that targets the HER2 receptor and is designed specifically to prevent the HER2 receptor from pairing (or dimerizing) with other HER receptors (EGFR/HER1, HER3, and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of pertuzumab to HER2 may also signal the body’s immune system to destroy the cancer cells.

The mechanisms of action of pertuzumab and trastuzumab are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of pertuzumab and trastuzumab is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.