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

 

by Anna van der Voort, Marte C. Liefaard, Mette S. van Ramshorst, Erik van Werkhoven, Joyce Sanders, Jelle Wesseling, Astrid Scholten, Marie Jeanne Vrancken Peeters, Linda de Munck, Sabine Siesling, Gabe S. Sonke 

 

The Breast: Published: July 13, 2022

 

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.

 

Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial

 

Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial

 

by José Manuel Pérez-García, Geraldine Gebhart, Manuel Ruiz Borrego, Agostina Stradella, Begoña Bermejo, Peter Schmid, Frederik Marmé, Santiago Escrivá-de-Romani, Lourdes Calvo, Nuria Ribelles, Noelia Martinez, Cinta Albacar, Aleix Prat, Florence Dalenc, Khaldoun Kerrou, Marco Colleoni, Noemia Afonso, Serena Di Cosimo, Miguel Sampayo-Cordero, Andrea Malfettone, Javier Cortés, Antonio Llombart-Cussac, PHERGain steering committee and trial investigators 

 

The Lancet Oncology: VOLUME 22, ISSUE 6, P858-871, JUNE 01, 2021

 

18F-FDG-PET identified patients with HER2-positive, early-stage breast cancer who were likely to benefit from chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab, and a reduced impact on global health status. Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy.

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: population based real world data from the Danish Breast Cancer Group (DBCG)

 

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: population based real world data from the Danish Breast Cancer Group (DBCG)

 

by Tobias Berg, Maj-Britt Jensen, Erik H. Jakobsen, Sami Al-Rawi, Julia Kenholm, Michael Andersson 

 

The Breast: VOLUME 54, P242-247, DECEMBER 01, 2020

 

Highlights

•Real world data on 215 patients with HER2-positive early breast cancer.

•SB3 (biosimilar trastuzumab) and pertuzumab with neoadjuvant chemotherapy.

•pCR in 56% and node conversion in 68% of the patients.

•pCR rate associated with ER-status and malignancy grade.

Abstract

Background

Dual blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy (NACT) has been increasingly used for HER2-positive tumours >2 cm and/or with positive axillary lymph nodes in order to evaluate pathologic response and obtain better surgical management. SB3 is a registered biosimilar trastuzumab approved following a phase III trial demonstrating similar efficacy in the neoadjuvant setting as trastuzumab. However, the study was done without pertuzumab.

Method

The database of the Danish Breast Cancer Group was used to extract data on all patients who started NACT with SB3 and pertuzumab between September 1, 2018 and August 31, 2019. The primary endpoint was pathological complete response (pCR) rate.

Results

In total 215 patients received NACT and dual blockade. The median age was 55 (24–81). NACT used was cyclophosphamide and epirubicin followed by weekly paclitaxel (62% on six cycles, 35% on eight cycles) or other chemotherapy followed by weekly paclitaxel (3%). Overall, 56% of patients achieved pCR. 60 of 88 node-positive patients pre-NACT achieved ypN0(i-) after neoadjuvant treatment. pCR rate was significantly associated with estrogen receptor status and malignancy grade. An association with CEP17/HER2-ratio was assessed.

Conclusion

Real world data on dual blockade with SB3 and pertuzumab in combination with NACT in a nationwide population-based study show a pCR rate comparable to that seen in previous clinical studies.