254O - Activity of neoadjuvant lapatinib (L) plus trastuzumab (T) for early breast cancer (EBC) according to PIK3CA mutations: Pathological complete respo...

Date 29 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anticancer agents
Translational Research
Breast Cancer
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological Therapy
Presenter Valentina Guarneri
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors V. Guarneri1, M.V. Dieci2, L. Carbognin3, A. Maiorana4, S. Bettelli4, G. Tortora3, P.F. Conte2, E. Bria3
  • 1Medical Oncology 2 And Department Ofsurgery, Oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS and University of Padova, 35128 - Padova/IT
  • 2Medical Oncology 2 And Department Ofsurgery, Oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS and University of Padova, Padova/IT
  • 3Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 4Department Of Pathology, Modena University Hospital, Modena/IT

Abstract

Aim

PIK3CA mutations are common in breast cancer. Our aim was to evaluate the correlation of PIK3CA mutational status with pCR in patients (pts) with HER2-positive EBC treated with neoadjuvant chemotherapy plus T, L or both.

Methods

PIK3CA mutations were evaluated in 121 pts randomized to neoadjuvant anthracyclines/taxane-based chemotherapy plus T, L, or both (CherLOB, Guarneri, JCO 2012). Exon 9 (E542K, E545K, E545A, E545G, Q546E, Q546K) and exon 20 (M1043I, H1047Y, H1047R, H1047L, G1049R, G1049S) PIK3CA mutations were evaluated on FFPE core biopsies by pyrosequencing. An event-based pooled analysis of trials reporting pCR events according to PI3KCA mutation status was performed; 95% confidence intervals (CI) were derived.

Results

PIK3CA status is available for 106 of the 121 CherLOB pts: 22 (20.8%) presented a PIK3CA mutation. In the whole population, pCR rates are similar in PIK3CA wild type (wt) and PIK3CA mutated (mut) pts (33.3% vs 22.7%; p = 0.34). However, for pts receiving T plus L (n = 41) the probability of achieving a pCR is higher in case of PIK3CA wt (48.5% vs 12.5%; p = 0.06). Data were cumulated with those deriving from the NeoALTTO (Baselga, ECCO-ESMO 2013) and GeparSixto (Loibl, SABCS 2013) trials (overall 702 pts). Results are shown in the table.

PIK3CA mut PIK3CA wt
Arms Pts pCR (95% CI) Pts pCR (95% CI)
Lapatinib 37 16.2% (4.3-28.1) 122 21.3% (14.0-28.5)
Trastuzumab 27 22.2% (6.5-37.9) 115 26.9% (18.8-35.1)
Lapatinib + Trastuzumab 84 21.4% (12.6-30.2) 317 45.5% (38.1-49.0)

The non-overlapping 95% CIs between pCR in pts receiving L plus T and those undergoing T or L may suggest a higher activity of the dual HER2 inhibition in pts without PI3KCA mutation. Conversely, no difference in pCR according to PIK3CA status seems to emerge among pts treated with single anti-HER2 agents.

Conclusions

In this hypothesis-generating analysis, the increased activity of the dual anti-HER2 blockade with T plus L seems limited to tumors not harboring PIK3CA mutations. A prospective validation testing the interaction according to the PIK3CA mutation is warranted.

Disclosure

All authors have declared no conflicts of interest.