In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. LB-63-LB-63
Abstract:
Background: The antibody-drug conjugate T-DM1 retains the mechanisms of action of trastuzumab, including HER2 targeting and interruption of HER2 signaling, and provides a means of delivering the cytotoxic agent DM1 directly to HER2-positive tumors. In the EMILIA study, T-DM1 demonstrated a statistically significant progression-free and overall survival (PFS, OS) benefit with less toxicity vs capecitabine plus lapatinib (XL) in patients (pts) with previously treated HER2-positive MBC. Activating mutations of PIK3CA may lead to resistance to currently available HER2-directed therapies. The relationship between treatment efficacy and tumor HER2 mRNA expression or PIK3CA mutation status was examined in pts from EMILIA. Methods: Tumor tissue collected for HER2 testing was also used for HER2 mRNA analysis by qRT-PCR and for PIK3CA assessment (with additional consent), using a PIK3CA Mutation Detection Kit. PFS and OS were analyzed for each BM subgroup using the Kaplan-Meier method and a Cox regression model. Results: Median mRNA concentration ratios and PIK3CA mutation frequency were similar across treatment arms and consistent with data previously reported. T-DM1 demonstrated superior PFS and OS vs XL in all BM subgroups. The hazard ratio of OS was less for pts with high ( & gt;median) vs low tumor HER2 mRNA levels. For XL-treated pts, PIK3CA mutations were associated with shorter median PFS and OS; PIK3CA mutations did not significantly affect T-DM1 treatment outcomes. Efficacy by BM Subgroup in EMILIA PFS T-DM1 XL Hazard ratioa 95% CI n Median PFS (months) n Median PFS (months) All patients 495 9.6 496 6.4 0.66 (0.56, 0.78) HER2 mRNA concentration ratio ≤Median 230 8.2 204 6.4 0.64 (0.50, 0.82) & gt;Median 197 10.6 235 6.9 0.65 (0.50, 0.85) PIK3CA mutation status Mutated 40 10.9 39 4.3 0.45 (0.25, 0.82) Wild type 93 9.8 87 6.4 0.74 (0.50, 1.10) OS T-DM1 XL Hazard ratio a 95% CI n Median OS (months) n Median OS (months) All patients 495 30.9 496 25.1 0.70 (0.56, 0.87) HER2 mRNA concentration ratio ≤Median 230 26.5 204 23.7 0.80 (0.59, 1.09) & gt;Median 197 34.1 235 24.8 0.53 (0.37, 0.76) PIK3CA mutation status Mutated 40 NE 39 17.3 0.26 (0.12, 0.57) Wild type 93 NE 87 27.8 0.68 (0.40, 1.15) aHazard ratios are based on unstratified analyses. CI, confidence interval; HER, human epidermal growth factor receptor; NE, not estimable; OS, overall survival; PIK3CA, phosphatidylinositide 3-kinase catalytic subunit α; PFS; progression-free survival; T-DM1, trastuzumab emtansine; XL, capecitabine + lapatinib Conclusions: Pts in all BM subgroups analyzed to date had longer PFS and OS with T-DM1 vs XL. Pts with tumors expressing high HER2 mRNA levels derived even greater OS benefit from T-DM1. XL-treated pts with PIK3CA mutations had worse outcomes than those with wild type PIK3CA. T-DM1-treated pts with PIK3CA mutations had a similar treatment benefit as those without, suggesting that the unique mechanism of action of T-DM1 may overcome PIK3CA mutation resistance. Citation Format: José Baselga, Sunil Verma, Jungsil Ro, Jens Huober, Ellie Guardino, Liang Fang, Steven Olsen, Gail Lewis Phillips, Sanne de Haas, Mark Pegram. Relationship between tumor biomarkers (BM) and efficacy in EMILIA, a phase III study of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC). [abstract]. In: Proceedings of the 104th Ann ual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-63. doi:10.1158/1538-7445.AM2013-LB-63
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-LB-63
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
