Adjuvant Pertuzumab-Based Regimen Sustains Clinical Benefit in 8-Year Follow-Up in HER2+ Early Breast Cancer

Sibylle Loibl, MD, PhD

The addition of pertuzumab (Perjeta) to standard adjuvant therapy of trastuzumab (Herceptin) and chemotherapy continued to reduce the risk of disease recurrence or death for patients with HER2-positive early breast cancer according to data from the third interim overall survival (OS) analysis of the phase 3 APHINITY trial (NCT01358877). Findings were presented during a 2022 ESMO Virtual Plenary.¹

At a median follow-up of 8.4 years, the overall survival (OS) rates were 92.7% in the pertuzumab-based therapy arm (n = 2400) vs 92.0% in the standard therapy arm (n = 2404) with a hazard ratio of 0.83 (95% CI, 0.68-1.02).

The benefit was most pronounced in patients with lymph node–positive disease, which investigators noted drove the OS benefit in the overall population. The 8-year OS rates were 91.1% vs 89.2% among patients with lymph node–positive disease in the pertuzumab (n = 1503) and standard therapy (n = 1502) arms, respectively. The unadjusted hazard ratio was 0.80 (95% CI, 0.63-1.00).¹

Among patients with node-negative disease who received adjuvant pertuzumab (n = 897), the 8-year OS rate was 96.4% vs 95.5% among those who received standard adjuvant therapy (n = 902). The unadjusted hazard ratio was 0.99 (95% CI, 0.64-1.55). At the time of the analysis, investigators reported that OS were immature, and a definitive OS analysis will be reported following 640 deaths.

Dual HER2-blockade was previously validated in the primary analysis of invasive disease-free survival (iDFS) of APHINITY. The results led to the approval of adjuvant pertuzumab in combination with trastuzumab and chemotherapy in 2017.²

APHINITY was a multicenter, randomized, double-blind, placebo-controlled trial which enrolled patients with HER2-positive, early breast cancer following surgery for primary tumor excision. Patients were randomly assigned 1:1 to receive trastuzumab and chemotherapy with or without the addition of pertuzumab.³ Individuals in the experimental arm received pertuzumab (840 mg loading dose followed by 420 mg) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously every 3 weeks for 1 year in combination with one of the following chemotherapy options: carboplatin, cyclophosphamide, docetaxel, doxorubicin, epirubicin, or paclitaxel.

The primary end point was iDFS and secondary end points include safety, OS, and health-related quality of life.^1,3

Updated, descriptive iDFS analyses were also reported during the plenary session by Sibylle Loibl, MD, PhD, associate professor of obstetrics and gynecology at the Goethe University of Frankfurt in Germany.

In the intention-to-treat population the 8-year iDFS rate was 88.4% vs 85.8% for pertuzumab and standard therapy, respectively, for a 2.6% absolute benefit.¹

The iDFS benefit was most pronounced in the lymph node–positive population, the 8-year iDFS rates were 86.1% and 81.2%, respectively, for an absolute benefit of 4.9%, and a reduction in the risk of disease recurrence or death of 28% (HR, 0.72; 95% CI, 0.60-0.87). Among those with node-negative disease, the 8-year iDFS rates were 92.3% vs 93.3%, respectively.

The most common iDFS event in the lymph node–positive patients included distant recurrence, which was reported in 8.7% of patients who received pertuzumab and 12.3% of patients who received standard therapy. Central nervous system metastases were reported in 2.9% of patients in both therapy arms. Locoregional breast cancer recurrence was reported as an iDFS event in 23 patients (1.5%) treated with pertuzumab vs 39 patients (2.6%) who received placebo. Other iDFS events included contralateral invasive breast cancer recurrence (0.9% vs 1.1%, respectively) and death without prior event (2.3% vs 2.5%).¹

The benefit of the addition of pertuzumab was observed regardless of hormone receptor status. Among those with hormone receptor–positive disease in the pertuzumab arm (n = 1536), the 8-year iDFS rate was 88.9% vs 86.1% for those in placebo arm (n = 1546). The hazard ratio was 0.75 (95% CI, 0.61-0.92). Among those with hormone receptor–negative disease the 8-year iDFS rates were 87.5% and 85.2%, in the experimental (n = 864) and control (n = 858) arms, respectively, with a hazard ratio of 0.82 (95% CI, 0.64-1.06).¹

“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 hormone receptor status,” Loibl said in a news release.¹ “The trend [toward] 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.”

In terms of toxicity, investigators noted that no new or unexpected safety signals were observed in the updated analysis.¹

References

1. 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 14, 2022. bit.ly/3uOrzSj
2. FDA grants regular approval to pertuzumab for adjuvant treatment of HER2-positive breast cancer. FDA. Updated December 17, 2021. Accessed July 14, 2022. bit.ly/3ccLvaU
3. A study of pertuzumab in addition to chemotherapy and trastuzumab as adjuvant therapy in participants with human epidermal growth receptor 2 (HER2)-positive primary breast cancer (APHINITY). ClinicalTrials.gov. Updated June 1, 2022. Accessed July 14, 2022. https://clinicaltrials.gov/ct2/show/NCT01358877