Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer

Nuciforo, P.; Townend, J.; Piccart, M.J.; Fielding, S.; Gkolfi, P.; El-Abed, S.; ... ; Cosimo, S. di (2023)

Article / Letter to editor

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.

• Breast cancer
• HER2-Positive
• Neoadjuvant
• Pathological complete response
• Long-term survival
• Dual anti-HER2 blockade

• All authors: Nuciforo, P.; Townend, J.; Piccart, M.J.; Fielding, S.; Gkolfi, P.; El-Abed, S.; Azambuja, E. de; Werutsky, G.; Bliss, J.; Moebus, V.; Colleoni, M.; Aspitia, A.M.; Gomez, H.; Gombos, A.; Coccia-Portugal, M.A.; Tseng, L.M.; Kunz, G.; Lerzo, G.; Sohn, J.; Semiglazov, V.; Saura, C.; Kroep, J.; Ferro, A.; Cameron, D.; Gelber, R.; Huober, J.; Cosimo, S. di
• Date: 2023-01-13
• Journal: European Journal of Cancer
• Volume: 181
• Pages: 92 - 101
• DOI: doi:10.1016/j.ejca.2022.12.020
• Link: https://www.sciencedirect.com/science/article/pii/S0959804922018317?via%...