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.; de Azambuja E.; 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.; Di Cosimo S. · European Journal of Cancer (2023) · DOI: 10.1016/j.ejca.2022.12.020

Resumen

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.