Survival outcomes of the NeoALTTO study: Updated results of a randomized multicenter phase III neoadjuvant trial

512 Background: In the neoadjuvant NeoALTTO trial dual HER2 blockade with lapatinib (L) plus trastuzumab (T) combined with weekly paclitaxel significantly increased the pathologic complete response rate (pCR) compared with either anti-HER2 agent alone plus paclitaxel. At first analysis pts with pCR had a better event free survival (EFS) and overall survival (OS) after median follow-up of 3.84 yrs. Methods: 455 pts with operable HER2-positive breast cancer were randomized to receive either L (n=154) 1500mg/day, T 4mg/kg loading dose followed by 2mg/kg/wk (n=149) or L 1000mg/day plus T (n=152) for 6 weeks followed by the assigned anti-HER2 treatment combined with paclitaxel weekly x 12. Following surgery pts received 3 cycles fluorouracil, epirubicin and cyclophosphamide q 3 weeks. The assigned anti-HER2 treatment was continued for 34 weeks thereafter. Primary endpoint was pCR (ypT0/is), secondary endpoints were EFS and OS and the association between pCR and OS analyzed by landmark analysis 30 weeks after randomization. Median follow-up was 6.7 years. Results: 6-yrs EFS rate was 67%/ 67%/74% with L/T/TL, respectively (L vs T HR 0.98 [95% CI 0.64–1.51] p=0.93; TL vs T HR 0.81 [95% CI 0.52–1.26] p=0.35). In the hormone receptor negative group 6- yrs EFS rate was 61%/ 63%/74% for the 3 groups, respectively (L vs T HR 1.09 [95% CI 0.61–1.95] p=0.76; TL vs T HR 0.81 [95% CI 0.44–1.51] p=0.52). OS at 6 yrs was 82%/79%/85% for L, T and TL, respectively (L vs T: HR 0.85 [95% CI 0.49-1.46] p=0.56; TL vs T HR 0.72 [95% CI 0.41-1.27] p=0.26). In landmark analyses, pts with a pCR had significantly higher 6-yrs EFS (77% /65%) and OS (89% /77%) compared to those without pCR, both overall and for the hormone receptor negative cohort. Conclusions: The updated results of the NeoALTTO study confirm the sustained survival benefits for pts who achieve a pCR. EFS and OS after 6 yrs did not differ significantly between the 3 treatment groups. The combination of T and L showed numerically higher EFS compared to T, especially in the hormone-receptor negative group. Clinical trial information: NCT00553358. [Table: see text]