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 Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Translational Research
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.