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.
