Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: 5-year outcomes of NSABP protocol B-41.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.501
ISSN1527-7755
AutoresAndré Robidoux, Gong Tang, Priya Rastogi, Charles E. Geyer, Catherine A. Azar, James N. Atkins, Louis Fehrenbacher, Harry D. Bear, Luis Báez-Díaz, Shakir Sarwar, Richard G. Margolese, William B. Farrar, Adam Brufsky, Henry R. Shibata, Hanna Bandos, Soonmyung Paik, Joseph P. Costantino, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark,
Tópico(s)Colorectal Cancer Treatments and Studies
Resumo501 Background: The primary aim of this randomized trial of neoadjuvant therapy in operable, HER2-positive breast cancer (BC) was to determine the effect on pathologic complete response (pCR) rates of substituting lapatinib (L) for trastuzumab (T) in combination with weekly paclitaxel (WP) following AC as well as adding L to T with WP following AC. Previously reported results showed pCR breast 52.5% for AC→WP+T, 53.2% for AC→WP+L, and 62% for AC→WP+TL. Planned secondary endpoints included 5-year recurrence-free interval (RFI) and overall survival (OS) and are reported here. Methods: All patients received standard AC q3wks x 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15 q28 days x 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, all patients received T to complete 52 wks of HER2-targeted therapy. 529 pts were randomized and 522 had follow-up. Median follow-up for this analysis was 5 years. Results: Five-year RFI was 84.3% for AC→WP+T, vs 78.6% for AC→WP+L (p=0.14: HR, 1.27; 95% CI, 0.74-2.20), and 90% for AC→WP+TL (p=0.33: HR, 0.66; 0.34-1.25). Five-year OS was 94.5% for AC→WP+T, vs 89.4% for AC→WP+L (p=0.11: HR, 1.52; 0.69-3.35), and 95.7% for AC→WP+TL (p=0.55: HR, 0.63; 0.24-1.67). Long-term outcomes correlated with pCR status. The HR for RFI (pCR breast vs non-pCR) was 0.45 (0.28-0.73; p=0.0009) for the entire study population, 0.64 (0.33-1.25; p=0.19) in the estrogen receptor (ER)-positive cohort, and 0.24 (0.12-0.49; p<0.0001) in the ER-negative cohort. The HR for OS was 0.28 (0.13-0.60; p=0.0004), 0.43 (0.11-1.65; p=0.20), and 0.16 (0.06-0.39; p<0.0001), respectively. Conclusions: Results of 5-year outcomes (RFI and OS) were consistent with previously reported findings regarding pCR status. While pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes and the improvement was more remarkable in the ER-negative subset. Support: GlaxoSmithKline Clinical trial information: NCT00486668.
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