The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

For patients with HER2-positive early breast cancer, the addition of pertuzumab to adjuvant trastuzumab and chemotherapy continued to show a significant improvement in invasive disease-free survival (IDFS) for patients at a high risk of recurrence at 6-years of follow-up; however, a survival benefit remains to be seen.

The results of the 6-year second interim OS analysis of the APHINITY trial ( Identifier: NCT01358877) were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas.

Based on the primary analysis of the APHINITY trial, pertuzumab in combination with trastuzumab and chemotherapy was approved in 2017 by the US Food and Drug Administration as an adjuvant regimen for patients with HER2-positive early breast cancer at high risk of recurrence.

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The APHINITY trial was initiated in November 2011 and included patients with HER2-positive early breast cancer who had previously had their tumor resected. In all, 2400 patients were randomly selected to receive adjuvant pertuzumab, trastuzumab, and chemotherapy and 2405 were assigned to receive placebo, trastuzumab, and chemotherapy.

The primary analysis revealed a 3-year IDFS rate benefit for the pertuzumab arm compared with the placebo arm, (94.1% vs 93.2%, respectively; hazard ratio [HR], 0.81; 95% CI, 0.66-1.00; P =.045), particularly for high risk patients — that is, patients with node-positive disease (HR, 0.77; 95% CI, 0.62-0.96; P =.019) or hormone receptor-negative disease (HR, 0.76; 95% CI, 0.56-1.04; P =.085).

However, with longer 6-year follow-up, an overall survival (OS) difference between patients who received pertuzumab vs placebo remains to be seen (94.8% vs 93.9%; HR, 0.85; 95% CI, 0.67-1.07; P =.17). For a result to be considered statistically significant in this study, a P value of .0012 was required.

The risk of relapse appeared consistent with the primary analysis: high-risk patients were at a reduced risk of relapse with pertuzumab. Specifically, patients with node-positive disease had a 4.5% absolute improvement in IDFS with pertuzumab compared with placebo (87.9% vs 83.4%, respectively; HR, 0.72; 95% CI, 0.59-0.87) and patients with hormone-receptor negative disease had a 2.5% absolute improvement (89.5% vs 87.0%, respectively; HR, 0.83; 95% CI, 0.63-1.10).

Patients with hormone receptor-positive disease also had an improved IDFS with pertuzumab compared with placebo (91.2% vs 88.2%; HR, 0.73; 95% CI, 0.59-0.92)

Patients with node-negative disease did not have an IDFS benefit with pertuzumab (HR, 1.02; 95% CI, 0.69-1.53).

“No benefit can be claimed in the node-negative population,” said Martine Piccart, MD, PhD, cofounder of Breast International Group and scientific director at the Institut Jules Bordet in Brussels, during a SABCS press conference.

“Many had hoped and assumed that with further follow-up, the benefit would grow,” Kathy Miller, MD, told Cancer Therapy Advisor about IDFS, the primary end point. Dr Miller is associate director of clinical research at Indiana University Melvin and Bren Simon Cancer Center and Ballvé Lantero Professor of Oncology and professor of medicine at Indiana University School of Medicine. (She was not involved in the trial.)

As for safety, the incidence of primary cardiac events was low: 0.8% in the pertuzumab arm and 0.3% in the placebo arm.

“Further follow-up will be very important to determine whether there is a survival benefit associated with pertuzumab administration in early HER2-positive breast cancer,” Dr Piccart said.

A third interim OS analysis is planned for 2022.

Disclosure: Roche contracted this research. Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of SABCS by visiting the conference page.


Piccart M, Procter M, Fumagalli D, et al. Interim overall survival analysis of APHINITY (BIG 4-11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-04.