Invasive Disease-Free Survival Improves With Perjeta Plus Standard Therapy in HER2-Positive Breast Cancer

Adding Perjeta (pertuzumab) to chemotherapy and trastuzumab did not significantly improve overall survival (OS) in women with HER2-positive early-stage breast cancer, although improvements were observed in invasive disease-free survival, according to a study published in the Journal of Clinical Oncology.

Findings from the APHINITY trial demonstrated that OS at six years was close to 95% in patients who added Perjeta to their treatment and those who did not, which further reinforces that combination therapy directed at HER2 and chemotherapy can lead to excellent outcomes in most patients with HER2-positive, early-stage breast cancer. Despite these findings, follow-up times beyond six years are needed to fully assess the OS benefit of this therapy.

Researchers from this trial previously reported findings from 45 months of follow-up, which demonstrated that adding Perjeta to adjuvant trastuzumab and chemotherapy significantly improved invasive disease-free survival (the time after treatment without signs of cancer) in patients with early-stage, HER2-positive breast cancer.

“Updated results from this (six-year) analysis strengthen the observation that patients with node-negative, HER2-positive early (breast cancer) show excellent (invasive disease-free survival) results up to six years from diagnosis when treated with standard adjuvant therapy without the addition of (Perjeta),” the study authors wrote.

Higher levels of HER2, a gene involved in the development of breast cancer, can lead to faster cancer growth and spread compared with other types of breast cancers. This gene is the second-most important target for therapy in breast cancer, with the first being the estrogen receptor, the study authors wrote. In breast cancer, overexpression of HER2 is found in approximately 15% to 20% of patients.

In this phase 3 trial, 4,805 patients with HER2-positive breast cancer were assigned either trastuzumab and Perjeta (2,400 patients) or trastuzumab and placebo (2,405 patients), both of which were administered for one year. Both groups also underwent chemotherapy.

At six years, OS was 95% in patients assigned Perjeta compared with 94% in those who were assigned placebo. There were 125 deaths during this time period.

The Perjeta group had fewer events related to invasive disease-free survival compared with the placebo group (91% versus 88%).

Patients in the node-positive group (breast cancer affecting the lymph nodes) benefited more from Perjeta regarding invasive disease-free survival compared with those assigned placebo (88% versus 83%). Those in the node-negative group (breast cancer not affecting the lymph nodes) did not benefit from the treatment.

When assessing invasive disease-free survival by HR status (which determines whether hormones are fueling cancer growth), patients assigned Perjeta with HR-positive cancer had a greater benefit than those assigned placebo (8.5% versus 11.7%). Patients with HR-negative cancer also benefitted from Perjeta compared with placebo (10.4% versus 12.4%).

Both treatment groups had a less than 1% rate of heart-related side effects, which was consistent with the earlier report from this study. In addition, no new safety issues were observed with either treatment.

“Continued follow-up of patients is important to fully assess OS benefit at the time-driven third interim OS analysis planned for 2022,” the study authors wrote.

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