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. 2022 Oct:65:110-115.
doi: 10.1016/j.breast.2022.07.005. Epub 2022 Jul 13.

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

Anna van der Voort  1 , Marte C Liefaard  2 , Mette S van Ramshorst  1 , Erik van Werkhoven  3 , Joyce Sanders  4 , Jelle Wesseling  4 , Astrid Scholten  5 , Marie Jeanne T F D Vrancken Peeters  6 , Linda de Munck  7 , Sabine Siesling  8 , Gabe S Sonke  9
Affiliations

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

Anna van der Voort et al. Breast. 2022 Oct.

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.

Keywords: ErbB2; HER2-Positive; Neoadjuvant chemotherapy; Non-metastatic breast cancer; Pertuzumab; Survival.

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Conflict of interest statement

Declaration of competing interest GSS reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen and consultancy fees paid to the institution from Biovica and Seagen. All other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flow diagram of included patients. Abbreviations: Neo-Adj, neoadjuvant; pCR, pathological complete response; BCSS, breast cancer specific survival; OS, overall survival.
Fig. 2
Fig. 2
Bar chart of pCR with adjusted odds ratios for pCR – overall and according to hormone receptor status. Abbreviations: pCR, pathological complete response; HR-positive, hormone receptor positive; HR-negative, hormone receptor negative; aOR, adjusted odds ratio: analyzed in multiple imputated data set and adjusted for age, clinical tumor stage, clinical nodal status, tumor grade, anthracyclines (yes/no), histology and in case of all patients: hormone receptor status.
Fig. 3
Fig. 3
Kaplan-Meier curves for breast cancer specific survival by lymph node status. A. Breast cancer specific survival per treatment group in clinical lymph node negative (cN0) patients; B. Breast cancer specific survival per treatment group in clinical lymph node positive (cN+) patients.
Fig. 4
Fig. 4
Forest Plot for Breast Cancer Specific Survival overall and within subgroups. Abbreviations: HR-positive, hormone receptor positive; HR-negative, hormone receptor negative; cT, clinical tumor stage; cN, clinical lymph node status; aHR, adjusted hazard ratio. ꝉTx patients are also included in cT0-2. #aHR for complete case analysis
See this image and copyright information in PMC

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