Long-Term Follow-Up Indicates Adjuvant Pertuzumab, Trastuzumab, and Chemo Reduces Recurrence in HER2+ Early Breast Cancer

Long-term follow-up from the phase 3 APHINITY trial (NCT01358877) highlighted a durable benefit among patients with lymph node–positive, HER2-positive early breast cancer at a high risk of recurrence regardless of hormone receptor status who were treated with adjuvant pertuzumab (Perjeta), trastuzumab (Herceptin), and chemotherapy vs trastuzumab and chemotherapy alone, according to a press released from Roche.

At a median follow-up of 8.4 years, those with lymph node–positive disease experienced a reduction in risk of recurrence or death of 28%, which translated to an 8-year invasive disease-free survival benefit rate of 4.9% (HR, 0.72; 95% CI, 0.60-0.87).

“The 8-year APHINITY results show the great progress made in treating this aggressive form of early breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, said in the press release. “HER2-positive breast cancers are more likely than other subtypes to recur following surgery, so targeted treatment is critical to provide the best chance for a cure.”

The trial had an actual enrollment of 4804 patients. Those in the experimental arm received an 840-mg loading dose of pertuzumab followed by subsequent doses of 420 mg, 8 mg/kg of trastuzumab every 3 weeks for 1 year, 500 mg/m² to 600 mg/m² of 5-fluorouracil for 3 to 4 cycles, 90 mg/m² to 120 mg/m² of epirubicin or 50 mg/m² of doxorubicin, and 500 mg/m² to 600 mg/m² of cyclophosphamide followed by 3 to 4 cycles of docetaxel or 12 cycles of paclitaxel at 80 mg/m², 4 cycles of doxorubicin at 60 mg/m² or 90 mg/m² to 120 mg/m² of epirubicin, 500 to 500 mg/m² of cyclophosphamide, and 3 to 4 cycles of docetaxel for 3 weeks or 12 cycles of paclitaxel weekly.

The mortality rate in the experimental arm was 7.0% vs 8.4% in the control arm (HR, 0.83; 95% CI, 0.68-1.02) and overall survival data were immature, statistically significant, and not yet reached. Moreover, the pertuzumab combination reduced the risk of recurrence or death by 23% in the overall population compared with the trastuzumab/chemotherapy combination (HR, 0.77; 95% CI, 0.66-0.91). Additionally, administration of the pertuzumab regimen following surgery yielded better disease-free survival (88.4%) vs the control group (85.8%), translating to an absolute benefit of 2.6%.

Efficacy with the regimen was observed regardless of hormone receptor status with a 25% reduction in risk of recurrence and 18% reduction in risk of death in the population vs the hormone receptor­–negative population (hormone receptor positive: HR, 0.75; 95% CI, 0.61-0.92; hormone receptor negative: HR, 0.82; 95% CI, 0.64-1.06).

Safety findings were consistent with previous reports, with no new or unexpected signals.

“These updated APHINITY data showed further reduction in the risk of cancer returning or death with a pertuzumab-based regimen in patients with [lymph node]–positive, HER2-positive early breast cancer, regardless of [HR] status. The trend towards a survival benefit was influenced by the [lymph node]–positive cohort and additional follow-up is very important to determine possible survival benefit and long-term safety of this regimen,” Sibylle Loibl, MD, PhD, chair of the German Breast Group (GBG) and the chief executive officer at the GBG Forschungs GmbH, concluded.

Reference

Eight-year data from APHINITY study show Roche’s Perjeta-based regimen continues to reduce the risk of disease returning for people with HER2-positive early breast cancer. News release. Roche. July 14, 2022. Accessed July 15, 2022. https://bit.ly/3PsYpQr