A Blockading Drug Proves its Merit as a
Treatment for Early-Stage Breast Cancer

Drug therapies that disrupt the abnormal signals driving cells to multiply have been key to one of the biggest breakthroughs in breast cancer treatment.

Over the past couple of decades, trastuzumab (also called Herceptin) has been a lifesaver for women with the breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2).

Used in combination with chemotherapy, it creates a complex “blockade” against the signals that cause disease.

But researchers are always looking for more effective treatments. Could another drug boost the blockade? And if so, how effective might it be?

The monoclonal antibody pertuzumab (also known by the brand name Perjeta) showed early promise and was the focus of the APHINITY randomized trial – which commenced in 2011 and involved 4,805 women, including 128 women from 15 participating institutions in Australia and New Zealand – and the subsequent follow-up research to better understand its impact over time. International teams have been reviewing the drug’s efficacy in combination with trastuzumab and chemotherapy.

Associate Professor Nicholas Wilcken, Director of Medical Oncology at Westmead and Breast Cancer Trials (BCT) Board Director, is part of the APHINITY research team. A new study published in May 2021 follows up on previous research showing that pertuzumab, used after surgery in conjunction with trastuzumab and chemotherapy in women with advanced cancer – treatable but not curable – was a valuable addition to a treatment regimen and increased survival time.

“That was an important proof of principle that the drug seems to be doing something,” explains Associate Professor Wilcken. “So, a logical next question to ask is, what about the women with potentially curable disease in an early setting? We’re already using chemotherapy plus Herceptin; let’s compare that with chemotherapy plus Herceptin plus pertuzumab.”

The new results tell a positive story for women with early-stage cancer. “It shows that the benefits of pertuzumab are modest, but are real,” says Associate Professor Wilcken.

The research confirms that the treatment is still effective and improving over time. The benefit for women with early-stage disease confined to the breast tissue – a cohort that does well with a combination of chemotherapy and trastuzumab – was relatively small.

But for women with early-stage breast cancer that had spread to the lymph nodes, the study’s results show a much more significant benefit in terms of recurrence and survival rates.

The APHINITY study also gave researchers greater confidence that pertuzumab caused no major side-effects for patients.

“Pertuzumab is very widely used in the metastatic setting, and it’s increasingly used in the early breast cancer setting, although unfortunately is not yet funded by the Pharmaceutical Benefit Scheme for early-stage disease,” says Associate Professor Wilcken.

“It also shows that, while there is the occasional blockbuster like trastuzumab, most improvements are modest, but they all add up over time.”

Publication

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years’ Follow-Up Martine Piccart, Marion Procter, Debora Fumagalli, Evandro de Azambuja, Emma Clark, Michael S. Ewer, Eleonora Restuccia, Guy Jerusalem, Susan Dent, Linda Reaby, Hervé Bonnefoi, Ian Krop, Tsang-Wu Liu, Tadeusz Pieńkowski, Masakazu Toi, Nicholas Wilcken, Michael Andersson, Young-Hyuck Im, Ling Ming Tseng, Hans-Joachim Lueck, Marco Colleoni, Estefania Monturus, Mihaela Sicoe, Sébastien Guillaume, José Bines, Richard D. Gelber, Giuseppe Viale, Christoph Thomssen, and for the APHINITY Steering Committee and Investigators. DOI: 10.1200/JCO.20.01204 Journal of Clinical Oncology 39, no. 13 (May 01, 2021) 1448-1457, epub 04/02/2021 https://ascopubs.org/doi/full/10.1200/JCO.20.01204