The addition of pertuzumab (Perjeta) to the previous standard of trastuzumab (Herceptin) plus chemotherapy as an adjuvant therapy for patients with operable HER2-positive early breast cancer continued to reduce the risk for recurrence and death, according to a 6-year analysis of the phase III APHINITY trial.1
In the descriptive analysis of invasive disease-free survival (IDFS) after 6 years of follow-up, the researchers found that the addition of pertuzumab reduced the relative risk for breast cancer recurrence by 24%, compared with placebo (HR, 0.76; 95% CI, 0.64-0.91). In addition, the regimen reduced the risk for death by 15% (HR, 0.85; 95% CI, 0.67-1.07; P = .170); however, of note, a P-value of .0012 is required for statistical significance for overall survival (OS), and therefore, survival data remain immature at this time.
In total, 221 patients in the pertuzumab arm (9.2%) and 287 patients in the placebo arm (11.9%) had an IDFS event. In the pertuzumab arm, this included 141 with a distant recurrent (5.9%), 28 with locoregional breast cancer recurrence (1.2%), 13 with contralateral invasive breast cancer recurrence (0.5%), and 39 deaths without a prior event (1.6%).
“Very importantly, after 74 months of follow-up, the clinical benefit of pertuzumab is seen regardless of hormone receptor status and no new cardiac safety issues emerged,” Martine Piccart, MD,PhD, cofounder of Breast International Group and scientific director at the Institut Jules Bordet in Brussels, said during a press briefing held at the San Antonio Breast Cancer Symposium, held December 10-14, in San Antonio, Texas.
In the 6-year updated analysis, the researchers also found that patients with node-positive disease induced an IDFS rate of 87.9% in the pertuzumab arm, compared with 83.4% in the placebo arm, representing a 4.5% improvement (HR, 0.72; 95% CI, 0.59-0.87). The addition of pertuzumab to the standard of care reduced relative risk of recurrence by 28% in this cohort.
In addition, this benefit was seen in patients with hormone receptor-positive disease (HR, 0.73; 95% CI, 0.59-0.92).
Of note, no new cardiac safety issues emerged in the updated analysis. Incidence of primary cardiac event remains <1% in both arms (0.8% with pertuzumab vs. 0.3% with placebo).
Between November 2011 and August 2013, in the randomized multi-center, double-blind, placebo-controlled study, 2,400 patients were randomly assigned to receive pertuzumab plus trastuzumab and chemotherapy and 2,405 patients received placebo plus the previous standard of care. Data cutoff for updated OS was June 19, 2019, with a median follow-up of 74.1 months.
IDFS served as the primary endpoint of the study. Secondary endpoints included IDFS with a second primary non-breast primary cancer that was included, disease free survival, OS, RFI, DRFI, safety, and health related quality of life. Stratification factors were nodal status, hormone receptor status, chemotherapy regimen, geographic region, and protocol version.
Data cutoff at the time of primary analysis was December 19, 2016, and median follow-up was 45.4 months.
Previous findings from the APHINITY trial showed that patients treated with pertuzumab had improved rates of estimated 3-year IDFS compared with those in the placebo arm (94.1% vs 93.2%, respectively). Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (HR, 0.81; 95% CI, 0.66-1.00; P = .045). However, the OS did not significantly differ between the 2 arms in the earlier analysis.2
Moreover, in the cohort of patients with node-positive disease, the 3-year rate of IDFS was 92.0% in the pertuzumab group, compared with 90.2% in the placebo group (HR, 0.77; 95% CI, 0.62-0.96; P = .02). In the cohort of patients with node-negative disease, the 3-year rate of IDFS was 97.5% in the pertuzumab group and 98.4% in the placebo group (HR 1.13; 95% CI, 0.68-1.86; P = .64).
“Further follow-up will be very important to determine whether there is a survival benefit associated with pertuzumab administration in HER2-positive breast cancer,” Piccart said, adding that a third interim analysis of time-driven OS is planned for 2.5 years from now.
1. Piccart M, Procter M, Fumagalli D, et al. Interim overall survival analysis APHINITY (BIG 4-11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer. Presented at: the San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. Abstract GS1-04.
2. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017; 377:122-131. doi:10.1056/NEJMoa1703643.