Adjuvant trastuzumab with or without pertuzumab after pathologic complete response to neoadjuvant HER2-targeted therapy and chemotherapy in HER2-positive breast cancer: A retrospective cohort study.

Abstract

e12503 Background: Neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) has been shown to improve rates of pathologic complete response (pCR). While current guidelines support one year of adjuvant trastuzumab, the incremental benefit of continuing dual HER2 blockade (T+P) in patients who achieve pCR remains uncertain. Given concerns regarding potential overtreatment, added toxicity, and cost, our study compared the survival outcomes in patients with pCR treated with adjuvant T+P versus T alone. Methods: We performed a single-center retrospective cohort study of patients with HER2-positive invasive breast cancer who achieved pCR after neoadjuvant dual anti-HER2 therapy and chemotherapy followed by definitive surgery and subsequently received adjuvant anti-HER2 therapy for a total of one year. Patients received adjuvant T alone or T+P, per treating physician preference. Outcomes included recurrence-free survival (RFS) and distant recurrence-free survival (DRFS), defined from date of surgery to recurrence or death; patients without events were censored at last follow-up. Associations with baseline functional status and comorbidity burden (ECOG performance status [PS], Charlson comorbidity index [CCI]) were evaluated using univariate Cox proportional hazards modeling. Results: A total of 128 patients who achieved pCR after neoadjuvant treatment were included; 109 received adjuvant T and 19 received T+P. Median age at diagnosis was 53.5 years. The groups did not differ significantly by race, sex, or baseline performance status (mean CCI of 1.57 vs 1.32). Patients receiving T+P had a higher prevalence of cN1 involvement at diagnosis. At a median follow-up of 9.28 years, 5-year RFS was 94% (95% CI, 89–98) with T and 95% (95% CI, 85–100) with T+P; 5-year DRFS was similarly high in both groups. On univariate analysis, CCI >2 was associated with worse RFS (HR 3.44, 95% CI, 1.15-10.2). Five-year overall survival was high across cohorts, with no statistically significant difference by adjuvant regimen (96% vs 100% for T and T+P), including among patients with higher comorbidity burden. Using Lexidrug-based pricing estimates, addition of pertuzumab increased estimated drug cost by ~$590 per cycle (~$6,500 over 11 cycles) compared with trastuzumab alone. Conclusions: Among patients with HER2-positive breast cancer achieving pCR following neoadjuvant dual HER2-targeted therapy and chemotherapy, long-term recurrence outcomes were excellent and were comparable between adjuvant trastuzumab alone versus continued dual HER2 blockade. These findings suggest the absolute benefit of adjuvant pertuzumab may be limited in this population who achieved a pCR and support further prospective evaluation of risk-adapted de-escalation strategies to minimize overtreatment and cost.