Adding pertuzumab to adjuvant chemotherapy and trastuzumab can improve long-term outcomes in patients with operable, HER2-positive early breast cancer, according to updated results from the phase 3 APHINITY trial. 

Pertuzumab provided a significant improvement in invasive disease-free survival (IDFS) and a trend toward improvement in overall survival (OS) at 8 years.  

“The trend towards a benefit for the overall survival was influenced strongly by the node-positive cohort, whereas the node-negative cohort didn’t show any differences,” said Sibylle Loibl, MD, PhD, of the German Breast Group Forschungs GmbH in Germany.  


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Dr Loibl presented these findings in an ESMO Virtual Plenary.

The phase 3 APHINITY trial (ClinicalTrials.gov Identifier: NCT01358877) included 4805 patients with HER2-positive, operable breast cancer who were randomly assigned to receive pertuzumab (n=2400) or placebo (n=2405), each in combination with chemotherapy and trastuzumab, within 8 weeks of surgery. 

IDFS Results

The study’s primary endpoint was IDFS, and the addition of pertuzumab significantly improved IDFS. The 8-year IDFS rate was 88.4% with pertuzumab and 85.8% with placebo (hazard ratio [HR], 0.77; 95% CI, 0.66-0.91). 

The benefit observed with pertuzumab was driven by patients with node-positive disease, Dr Loibl noted. In the node-positive cohort, the 8-year IDFS was 86.1% with pertuzumab and 81.2% with placebo (HR, 0.72; 95% CI, 0.60-0.87). There was no benefit in the node-negative cohort (92.3% vs 93.3%; HR, 1.01; 95% CI, 0.72-1.42). 

Among patients with hormone receptor-positive disease, the 8-year IDFS was 88.9% with pertuzumab and 86.1% with placebo (HR, 0.75; 95% CI, 0.61-0.92). In the hormone receptor-negative cohort, the 8-year IDFS rate was 87.5% with pertuzumab and 85.2% with placebo (HR, 0.82; 95% CI, 0.64-1.06). 

Dr Loibl said these results suggest that hormone receptor status should not guide pertuzumab treatment decisions, but patients with node-positive disease derive a benefit from pertuzumab.

OS and Safety

There was no significant difference in OS between the treatment arms. The 8-year OS rate was 92.7% with pertuzumab and 92.0% with placebo (HR, 0.83; 95% CI, 0.68-1.02; P =.078).

However, there was an OS benefit with pertuzumab among patients with node-positive disease. The 8-year OS rate was 91.1% with pertuzumab and 89.2% with placebo (HR, 0.80; 95% CI, 0.63-1.00). 

There was no significant difference in OS between treatment groups in the node-negative cohort. The 8-year OS rate was 95.5% with pertuzumab and 96.4% with placebo (HR, 0.99; 95% CI, 0.64-1.55).

Primary cardiac adverse events occurred in less than 1% of patients in both treatment arms. Heart failure (class III with a left ventricular ejection fraction decrease) occurred in 0.7% of patients in the pertuzumab arm and 0.2% of those in the placebo arm. There were 3 cardiac deaths in the pertuzumab arm and 4 in the placebo arm. 

Disclosures: This study was supported by Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Loibl S, Jassem J, Sonnenblick A, et al. Adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years’ follow-up. ESMO Virtual Plenary; July 14-15, 2022. Abstract VP6-2022.