Findings from the phase 3 APHINITY study show that the combination pertuzumab, trastuzumab, and chemotherapy improves invasive disease-free survival compared with trastuzumab and chemotherapy alone in patients with lymph node-positive, HER2-positive early breast cancer.
Pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy when given as an adjuvant, intravenous (IV) treatment vs trastuzumab, chemotherapy, and placebo, continue to show benefit as treatment for patients with lymph node-positive, HER2-positive early breast cancer, who are at high risk of recurrence, according to Roche.1
Findings come from the third interim overall survival (OS) analysis of the APHINITY study (NCT01358877) where patients were evaluated after a median follow-up of 8.4 years to examine updated results on invasive disease-free survival (iDFS) and safety.
In patients with lymph node-positive disease, investigators observed a 28% reduction in the risk of recurrence or death, as well as an absolute benefit of 4.9% at 8 years (HR, 0.72; 95% CI, 0.60-0.87). These data were presented at the European Society for Medical Oncology (ESMO) Virtual Plenary and showed the safety profile to be consistent with previous studies.
“The 8-year APHINITY results show the great progress made in treating this aggressive form of early breast cancer,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development of Roche, 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.”
Within the global, phase 3, randomized, double-blind, placebo-controlled, 2-arm study evaluating the efficacy and safety of the combination of pertuzumab, trastuzumab, and chemotherapy, compared to trastuzumab and chemotherapy, 4,804 patients with operable HER2-positive early breast cancer were enrolled.2
Enrollment was open to adults with histologically confirmed non-metastatic operable primary invasive HER2-positive carcinoma of the breast who had an ECOG performance status less than or equal to 1 and known hormone receptor status. Additionally, the interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks, and the first cycle of chemotherapy must be administered to patients within 7 days of randomization or on day 56.
In the experimental arm, patients received pertuzumab at a dose of 840 mg followed by 420 mg and 8 mg/kg of trastuzumab followed by 6 mg/kg via intravenous (IV) infusion every 3 weeks for 1 year in combination with an IV chemotherapy regimen. Those enrolled in the placebo comparator arm were administered placebo matching the dose of pertuzumab IV and trastuzumab at 8 kg/mg, then 6 mg/kg every 3 weeks for 1 year in addition to an IV chemotherapy regimen.
The primary end point of the trial was iDFS, defined as the time a patient lives without recurrence of invasive breast cancer or death from any cause after post-surgery treatment. Secondary end points consisted of cardiac and overall safety, OS, and health-related quality of life.
Those enrolled in the study will be continuously followed up for 15 years from when the last patient was enrolled in the study.
After eight years, results of the trial showed that with the pertuzumab-based regimen, fewer deaths were observed (168 [7.0%]) compared with (202 [8.4%]) in the trastuzumab plus chemotherapy arm (HR, 0.83; 95% CI, 0.68-1.02). However, the OS data remains immature and statistical significance has not yet been reached.
Patients who received the pertuzumab-based regimen continue to see a reduced risk of breast cancer recurrence or death by 23% vs those administered trastuzumab, chemotherapy and placebo (HR, 0.77; 95% CI, 0.66-0.91).
More patients remained disease-free if they received post-surgery treatment with the pertuzumab-based regimen compared with those treated with trastuzumab, chemotherapy and placebo, showing an absolute benefit of 2.6% (88.4% vs 85.8%, respectively).
Participants at high risk of cancer recurrence, mostly those with lymph node-positive disease who are in highest need of more efficacious treatments, showed to have the greatest benefit with a 28% reduction in the risk of recurrence or death with the pertuzumab-based regimen (HR, 0.72; 95% CI, 0.60-0.87). This resulted in an absolute benefit of 4.9% (86.1% vs 81.2%, respectively).
The effect of the pertuzumab-based regimen was seen regardless of hormone receptor status and a 25% and 18% reduction in the risk of recurrence or death in people with hormone receptor-positive disease and those with hormone receptor-negative disease, respectively (HR, 0.75; 95% CI, 0.61-0.92 and HR, 0.82; 95% CI 0.64-1.06). These data were consistent with that seen in previous analyses.
Further, the safety profile remained consistent with previous studies. No new cardiac safety issues emerged from this interim analysis as the incidence of primary cardiac events remained less than 1% in the pertuzumab-based vs the trastuzumab plus chemotherapy arm (0.8% vs 0.4%). Additionally, no other new or unexpected safety signals were identified.
“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. 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,” stated Sibylle Loibl, PhD, chair of the German Breast Group, chief executive officer of the German Breast Group Forschungs GmbH, and APHINITY study chair, in the press release.