Pathological Complete Response Linked to Neoadjuvant Anti-HER2 Survival

Pathological complete response predicts improved outcomes for early breast cancer patients given neoadjuvant HER2-targeted therapy

medwireNews: Secondary analysis from the NeoALLTO trial suggests that women with early breast cancer who achieve a pathological complete response (pCR) after neoadjuvant anti-HER2 treatment have better event-free and overall survival than those who do not.

Initial study results showed that patients given combined lapatinib and trastuzumab plus paclitaxel, were significantly more likely to achieve a pCR than those given paclitaxel with lapatinib or trastuzumab as single agents, explain Evandro de Azambuja, from Institut Jules Bordet in Brussels, Belgium and co-investigators.

Now, the team reports that after an average follow-up of 3.77 years, 3-year event-free survival was comparable in the 152 patients given combined anti-HER2 treatment, the 154 patients given only lapatinib and the 149 patients given only trastuzumab (84 vs 78 and 76%, respectively).

And after a median survival follow-up of 3.84 years, there was no significant difference between the lapatinib and trastuzumab only groups with regard to 3-year overall survival (93 vs 90%) or between patients given combined HER2 treatment versus trastuzumab alone (95 vs 90%).

Landmark analyses conducted at week 30 indicated that women who achieved a pCR were significantly more likely than those who did not to achieve 3-year event-free and overall survival, with hazard ratios of 0.38 and 0.35, respectively.

However, the relationship between pCR and survival did not reach significance for any specific treatment arm.

In a comment in The Lancet Oncology, Heikki Joensuu, from the University of Helsinki in Finland, says that this may mean “pathological complete response might not be associated with better survival outcomes for patients treated with lapatinib plus trastuzumab than for patients treated with either drug alone.”

He adds: “Time will tell whether dual targeting of HER2 with other drugs is more successful-but at present, trastuzumab combined with chemotherapy remains the standard of care.”

Nevertheless, Evandro de Azambuja and team conclude: “These findings support the neoadjuvant approach to test new drugs in early breast cancer, allowing rapid assessment of efficacy, because pathological complete response is a short-term outcome and the number of patients included in neoadjuvant trials is not large.

“If this approach is shown to be useful, it could expedite development and approval of new treatments in patients with HER2-positive early breast cancer”, they hope.

Reference

de Azambuja E, Holmes A, Piccart-Gebhart M, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; Early online publication 15 August. doi:10.1016/S1470-2045(14)70320-1

Joensuu, H. Dual targeting of HER2 with lapatinib and trastuzumab. Lancet Oncol 2014; Early online publication 15 August. doi:10.1016/S1470-2045(14)70342-0

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