Highlights
- •Neoadjuvant lapatinib and/or trastuzumab treatment optimisation is the longest-lasting neoadjuvant study in human epidermal growth factor receptor-2 (HER2)-positive breast cancer.
- •Patients with pathological complete response (pCR) show better survival than those without pCR.
- •This gain is especially seen in hormone-receptor-negative or dual anti-HER2 subgroups.
- •pCR benefit is durable as hazard risk is low (er) even after 5–10 years from surgery.
Abstract
Background
Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the
rate of pathological complete response (pCR) compared to single blockade when added
to chemotherapy. However, limited data exist on the long-term impact on survival of
the additional increase in pCR.
Methods
Neoadjuvant lapatinib and/or trastuzumab treatment optimisation (NCT00553358) is an
international, randomised, open-label, phase III study investigating the addition
of lapatinib to chemotherapy plus trastuzumab in HER2-positive early BC. Ten-year
event-free survival (EFS), overall survival (OS) and safety were assessed on intention-to-treat
population. The association between pCR and EFS or OS was investigated in landmark
population.
Results
A total of 455 patients were randomised to receive lapatinib (154), trastuzumab (149) or
the combination (152). Ten-year EFS estimates were 63% (95% confidence interval [CI],
54%–71%) in the lapatinib group, 64% (95% CI, 55%–72%) in the trastuzumab group and
67% (95% CI, 58%–74%) in the combination group. Ten-year OS rates were 76% (95% CI,
67%–83%), 75% (95% CI, 66%–82%) and 80% (95% CI, 73%–86%) in the lapatinib, trastuzumab and
combination groups, respectively. Women who achieved a pCR had improved EFS (hazard
ratio 0.48, 95% CI, 0.31–0.73) and OS (hazard ratio 0.37, 95% CI, 0.20–0.63) compared
with those who did not. The numerical difference in survival according to pCR status
was greater in women treated with the combination and those with hormone-receptor-negative
tumours. There were no new or long-term safety concerns.
Conclusions
Patients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2,
irrespective of treatment arm. Patients who achieve pCR have significantly better
outcomes than patients without pCR.
Keywords
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Article info
Publication history
Published online: January 09, 2023
Accepted:
December 20,
2022
Received in revised form:
December 20,
2022
Received:
November 7,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
