Complete response to neoadjuvant treatment improves survival in early breast cancer

Women with HER2+ early breast cancer who achieved pathologic complete response (pCR) on neoadjuvant treatment had improved overall survival (OS) and event-free survival (EFS) outcomes, according to final analysis results of the phase III NeoALTTO, BIG 1-06 trial.

“Patients who achieved a pCR had significantly better long-term survival compared to those who did not achieve pCR,” commented principal investigator Dr Paolo Nuciforo from the Vall d'Hebron Institute of Oncology, Barcelona, Spain.

“Although OS rates did not differ significantly between the three treatment groups, nearly twice as many patients achieved pCR if they received both drugs [trastuzumab-lapatinib], 51 percent compared to 27.1 percent of patients receiving only one drug [trastuzumab or lapatinib] in the other two arms of the study combined,” he said.

Participants in this multicentre, open-label trial were 455 patients with HER2+ early breast cancer. They were randomized to receive neoadjuvant oral lapatinib (1,500 mg/day; n=154), intravenous trastuzumab (4 mg/kg loading dose followed by 2 mg/kg; n=149), or both (lapatinib at 1,000 mg/day and trastuzumab [same dose as monotherapy]; n=152) for 6 weeks. Following this, they received their assigned anti-HER2 treatments plus paclitaxel (80 mg/m²) for 12 weeks.

After surgery, patients received fluorouracil, epirubicin, and cyclophosphamide for three cycles, followed by the assigned neoadjuvant anti-HER2 treatments for 34 weeks. Patients were followed up for a median 9.7 years.

EFS at 9 years was 63, 65, and 69 percent in the lapatinib alone, trastuzumab alone, and trastuzumab-lapatinib groups, respectively. There was no significant difference in EFS between the lapatinib alone (hazard ratio [HR], 1.01, 95 percent confidence interval [CI], 0.66–1.52; p=0.98) and the lapatinib-trastuzumab group (HR, 0.88, 95 percent CI, 0.57–1.34; p=0.55) compared with trastuzumab alone. [EBCC 2020, abstract ORAL-023]

Nine-year OS rates were also comparable between the lapatinib alone (77 percent), trastuzumab alone (76 percent), and trastuzumab-lapatinib groups (80 percent). Again, OS did not significantly differ between patients on lapatinib alone (HR, 0.96, 95 percent CI, 0.58–1.60; p=0.88) or trastuzumab-lapatinib (HR, 0.79, 95 percent CI, 0.46–1.34; p=0.38) vs trastuzumab alone.

Landmark analysis at 30 weeks post-randomization showed that patients who achieved pCR had greater 9-year EFS compared with those who did not achieve pCR (77 percent vs 61 percent; HR, 0.48, 95 percent CI, 0.31–0.73; p=0.0008). Nine-year OS was also improved in those who did vs did not achieve pCR (88 percent vs 72 percent; HR, 0.37, 95 percent CI, 0.20–0.63; p=0.0004).

Subgroup analysis showed that these improvements with pCR were significant among patients with hormone receptor-negative disease (EFS: 76 percent vs 54 percent [no pCR]; HR, 0.43, 95 percent CI, 0.25–0.73; OS: 87 percent vs 68 percent [no pCR]; HR, 0.33, 95 percent CI, 0.15–0.66, p=0.002 for both) and in the trastuzumab-lapatinib group (EFS: HR, 0.35, 95 percent CI, 0.16–0.71; p=0.004; OS: HR, 0.22, 95 percent CI, 0.07–0.58; p=0.002).

“[These findings] validate pCR as an early indicator of long-term outcome for HER2+ disease and could help doctors decide on the best treatment,” said Nuciforo.

“At present, all women with HER2+ breast cancer receive toxic adjuvant chemotherapy after anti-HER2 neoadjuvant treatment to reduce the risk of recurrence after surgery. However, not all women have the same risk. If we could predict, for example with pCR, which patients are at high risk of their cancer recurring in 3, 5, or 10 years, we could give more aggressive adjuvant therapies only to these women and not to those women who have achieved pCR and are at low risk of recurrence,” he suggested.