SAN ANTONIO—Survival follow-up analysis of the NeoALTTO study presented at the 2013 San Antonio Breast Cancer Symposium has found patients with HER2-positive breast cancer and pathologic complete response (pCR) to neoadjuvant lapatinib, trastuzumab, or their combination had significantly better rates of event-free survival (EFS) and overall survival (OS) than those without pCR, regardless of treatment arm.

The phase 3 randomized NeoALTTO—Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization—trial is evaluating whether dual HER2 blockade with the combination of trastuzumab and lapatinib, given with standard paclitaxel chemotherapy, can induce pCRs compared with either agent alone with paclitaxel.

Previously, results showed that 51.3% of patients randomly assigned to neoadjuvant trastuzumab plus lapatinib had a pCR compared with 29.5% of those who received trastuzumab alone and 24.7% with lapatinib alone (both P < 0.01), said Martine Piccart-Gebhart, MD, PhD, chair of the Breast International Group (BIG), Brussels, Belgium.

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The current question being addressed is, “does the incremental gain in pCR observed with dual HER2 blockade translate into improved EFS and OS?”Dr. Martine Piccart-Gebhart

The follow-up landmark analysis by polymerase chain reaction found that for all patients, 3-year EFS rate was 86% for those with pCR compared with 72% for those without pCR (hazard ratio [HR], 0.33; 95% CI: 0.22-0.63; P = 0.0003). For patients with hormone receptor–positive disease, the HR was 0.50 compared with 0.34 for those with hormone receptor–negative disease.

The 3-year landmark OS rate was 94% in patients with pCR compared with 87% without pCR (HR, 0.35; 95% CI: 0.15-0.70; P = 0.005). A difference in OS among those hormone receptor–positive versus negative was also observed: HR, 0.85 versus HR, 0.29. These results provide further evidence that HER2-positive/hormone receptor–positive and HER2-positive/hormone receptor–negative subgroups are two different diseases.

“Our new analysis shows that the improved pathologic complete response rates seen in the hormone receptor–negative/HER2-positive subgroup seem to translate into better long-term outcomes for patients,” she said. “I believe that these results, if confirmed in the large ALTTO adjuvant trial (to be reported at the 2014 ASCO meeting) will impact the process of drug development in the field of early HER2-positive breast cancer.”

Data are needed from ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization), which is testing efficacy of treatment with trastuzumab plus lapatinib after breast cancer surgery—because NeoALTTO is underpowered to make survival comparisons, Dr. Piccart-Gebhart said.

“If the results of both studies are in line with each other, and depending on the strength of the ALTTO results, we could witness a new standard of care for managing primary HER2-positive breast cancer,” she predicted.

The study enrolled 455 patients with HER2-positive primary breast cancer with tumors greater than 2 cm in diameter at 86 sites in 23 countries in Europe, Asia, North and South America, and South Africa.

Patients were randomly assigned to lapatinib 1,500 mg/day (n = 154), trastuzumab 4 mg/kg intravenous (IV) loading dose followed by 2 mg/kg IV weekly (n = 149), or lapatinib 1,000 mg/day with trastuzumab (n = 152) alone for 6 weeks followed by 12 additional weeks concurrently with paclitaxel followed by surgery and postsurgical adjuvant chemotherapy. This was then followed by the same HER2-targeted therapy as in the neoadjuvant phase to complete 52 weeks.

A follow-up analysis is planned in 2.5 years as well as for 10 years after the last patient is randomly assigned to treatment.

These data support pCR as an acceptable surrogate end point, Dr. Piccart-Gebhart said.

The adverse events were found to be consistent with the known safety profile of lapatinib and/or trastuzumab.


  1. Piccart-Gebhart M. S1-01. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.