VP6-2022: Adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years' follow-up
S. Loibl; J. Jassem; A. Sonnenblick; G. Viale; J. Bines; M. Piccart
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From Nov 2011 until Aug2013, the randomized, phase III, double-blind APHINITY trial enrolled 2400 patients with HER2+, operable breast cancer assigned to receive pertuzumab (P) added to adjuvant trastuzumab (T) and chemotherapy and 2405 to receive placebo plus T and chemotherapy.
The primary analysis demonstrated that adding P to T plus chemotherapy statistically significantly improved invasive disease-free survival (IDFS) leading to a new standard of care for high-risk patients. Two pre-specified analyses of overall survival (OS) did not reach statistical significance. We now report the results of the 3rd pre-specified analysis of OS and updated descriptive analyses of IDFS.
With 8.4 years of median follow-up (clinical cut-off date 10 Jan 2022) fewer deaths were observed in the P group [168 (7.0%) vs 202 (8.4%)]. Statistical significance (p-value < 0.0060 required) was not reached. The hazard ratio for OS is 0.83 [95% CI 0.68-1.02 (p=0.078)]; 8-year OS are 92.7% vs 92.0% (0.7% difference). Updated IDFS results based on 609 events in the ITT population are: hazard ratio 0.77 [95% CI 0.66-0.91]; 8-year IDFS are 88.4% vs 85.8% (2.6% difference), respectively. The difference was due mainly to the reduction in distant (6.2% vs 8.5%) and locoregional (1.3% vs 2.4%) BC relapses. The node positive (N+) cohort continues to derive clear IDFS benefit from the addition of P: hazard ratio 0.72 (95% CI 0.60-0.87). The benefit in terms of 8-year IDFS is 4.9% [86.1% vs 81.2%]. In the N- cohort, the IDFS hazard ratio is 1.01 with >92% of patients being event-free in both arms at 8 years. IDFS benefit of P is seen in both the HR- and HR+ cohorts: IDFS hazard ratio for HR- is 0.82 (95% CI 0.64-1.06). IDFS hazard ratio for HR+ is 0.75 (95 % CI 0.61-0.92). No new cardiac safety concerns emerged.
After 8.4 years of median follow-up, no statistically significant difference in OS was found. IDFS benefit of P in HER2+ early BC is maintained, with the benefit continuing in the N+ cohort, regardless of HR status. HR status should not guide P treatment decisions. Continued follow up of patients is needed to determine possible survival benefit and long-term safety of adding adjuvant P to T. The final OS analysis is planned when 640 deaths have occurred.