Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival. (October 2022)

• Record Type: Journal Article
• Authors: van der Voort, Anna; Liefaard, Marte C.; van Ramshorst, Mette S.; van Werkhoven, Erik; Sanders, Joyce; Wesseling, Jelle; Scholten, Astrid; Vrancken Peeters, Marie Jeanne T.F.D.; de Munck, Linda; Siesling, Sabine; Sonke, Gabe S.
• Is Part Of: Breast. Volume 65(2022)
• Page Start: 110
• Page End: 115
• Publication Date: 2022-10
• Subjects: Non-metastatic breast cancer -- HER2-Positive -- ErbB2 -- Pertuzumab -- Neoadjuvant chemotherapy -- Survival; Adj adjuvant -- aHR adjusted hazard ratio -- ALD axillary lymph node dissection -- aOR adjusted Odds ratio -- BCS breast conserving surgery -- BCSS breast cancer specific survival -- CBS Statistics Netherlands -- cN clinical lymph node status -- cT clinical tumor stage -- EMA European Medicines Agency -- EFS even-free survival -- ER estrogen receptor -- US Food and Drug Administration (FDA) -- HER2 human epidermal growth factor receptor 2 -- HR hormone receptor -- MARI marking axillary lymph nodes with radioactive iodine seeds -- NCR Netherlands Cancer Registry -- Neo-Adj neoadjuvant -- NST invasive carcinoma of no special type -- OS overall survival -- PALGA Dutch Nationwide Pathology Databank -- pCR pathologic complete response -- PR progesterone receptor -- SNP sentinel node procedure -- T-DM1 trastuzumab emtansine; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2022.07.005
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background: Pathologic complete response (pCR) rates in early stage HER2-positive breast cancer improved after pertuzumab was added to neoadjuvant treatment. However, survival benefit is less-well established and seems mostly limited to node-positive patients. We used national cancer registry data to compare outcomes of patients treated with and without pertuzumab. Methods: We identified stage II-III HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based chemotherapy between November 2013 until January 2016 from the Netherlands Cancer Registry. During that period pertuzumab was only available in the 37 hospitals that participated in the TRAIN-2 study. Missing grade and pCR-status were obtained from the Dutch Pathology Registry (PALGA) and cause of death from Statistics Netherlands. We used multiple imputation to impute missing data, multivariable logistic regression to evaluate the association between pertuzumab and pCR (ypT0/is, ypN0) and multivariable Cox regression models for overall survival and breast cancer specific survival (BCSS). Results: We identified 1124 patients of whom 453 received pertuzumab. Baseline characteristics were comparable, although tumor grade was missing more often in patients treated without pertuzumab (12% vs. 2%). Pertuzumab improved pCR rates (41% vs 65%, adjusted odds ratio [aOR] 2.91; 95% CI:2.20–3.94). After a median follow-up of 6.0 years, 5-year BCSS rates were 95% and 98% respectively (adjusted hazard ratio [aHR]: 0.58; 95% CI:0.36–0.95). Younger patients derived more benefit from pertuzumab, but no other significant interactions were found. Conclusion: These results support earlier data of a small survival benefit with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy which is most meaningful in younger patients. Highlights: The benefit of adding pertuzumab to the (neo)adjuvant treatment of lymph node negative and HR+/HER2+ patients remains unclear. Pertuzumab increases pCR rate from 41% to 65% in stage II-III HER2+ breast cancer. 5-year BCSS is 95% and 98% in patients treated without and with pertuzumab, respectively. Patients <50 years benefit most from the addition of pertuzumab. Survival benefit of pertuzumab is more evident in patients with higher stage, but independent of HR-status.