322PD - A treatment-interaction analysis balancing pathological complete responses (PCR) and cardiotoxicity of single-(S)/dual-(D) HER2 inhibition and neoad...

Date 01 October 2012
Event ESMO Congress 2012
Session Breast cancer, locally advanced and metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Complications of Treatment
Breast Cancer, Locally Advanced
Presenter Emilio Bria
Authors E. Bria1, M. Bonomi2, J. Furlanetto1, S. Pilotto1, L. Carbognin1, F. Massari3, E. Lucchini1, D. Melisi1, D. Giannarelli4, G. Tortora3
  • 1Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 2Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 3Oncologia Medica, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 4Medical Oncology, Regina Elena National Cancer Institute, Roma/IT

Abstract

Purpose

Given the toxicity drawbacks potentially related to the combination of anthracylines and a D-HER2 inhibition, a treatment interaction analysis of the available randomized trials was accomplished.

Methods

pCR (breast + axilla), breast conserving surgery (BCS), grade 3-4 neutropenia/cardiotoxicity, and febrile neutropenia (FN), events were extracted from papers/presentation and cumulated according to a random-effect model; 95% confidence intervals (CI) were derived. A sensitivity analysis according to S/D HER2 inhibition, hormonal receptors (HRs) and CT (anthracyclines-taxanes: anthra-TAX; TAX alone) was accomplished to test for interaction. Absolute differences (AD) with 95% CIs, and the number of pts needed to treat/harm (NNT/NNH) for 1 to benefit were calculated to derive the Likelihood of being Helped or Harmed (LHH).

Results

8 trials (2092 pts) with 1955 pts treated with anti-HER2 therapy (Trastuzumab, Lapatinib and Pertuzumab), were gathered; pCR rates according to HER2 inhibition follow:

CT HER2-Inhibition Rates (95% CI) Interaction (p) NNT
Anthra-TAX S 37.0 [34.0, 40.0] 0.22 2.7
D 44.3 [33.3, 55.2] 2.2
TAX S 21.7 [18.1, 25.3] <0.0001 4.6
D 42.4 [36.4, 48.5] 2.3
pCR rates were significantly higher in the HRs negative population, regardless of the HER2 inhibition and CT backbone (Neg. vs. Pos. Anhtra-TAX [S] AD 9.4%, p = 0.002; TAX [S] AD 15.3% p < 0.0001; TAX [D] AD 28%, p < 0.0001). With regard to CT, a significant interaction (p < 0.0001) in favour of adding Anthra to TAX was found in the context of S-HER2 inhibition subgroup with regard to pCR (AD 15.4%) and BCS (AD 10.8%) with no interaction in the D-subgroup. No significant differences in FN and cardiotoxicity were found according to HER2 inhibition and CT. In the Anhtra-TAX [S] population weighted for cardiotoxity, LHH was 77.

Conclusions

On the basis of the available data, anthracyclines should be considered for O/LABC patients receiving TAX-based CT plus HER2 inhibition, given the likelyhood 70-times greater to achieve pCR than to be harmed by clinically meaningful cardiotoxicity.

Disclosure

All authors have declared no conflicts of interest.