Trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy in resectable HER2+ esophageal adenocarcinoma patients: an update on survival and...

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Oesophageal Cancer
Presenter Charlotte Stroes
Citation Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247
Authors C.I. Stroes1, A. Creemers1, R.J. Bennink2, S. Schokker1, R.H.A. Verhoeven3, S.L. Meijer4, K.K. Krisnadath1, M. van Oijen1, G. Creemers5, M.J.C. van der Sangen6, L.V. Beerepoot7, J. Heisterkamp8, M. Los9, M. Slingerland10, A. Cats11, G.A.P. Hospers12, M. Bijlsma1, M.I. van Berge Henegouwen13, M. Hulshof14, H.W.M. van Laarhoven1
  • 1Medical Oncology, Amsterdam UMC, University of Amsterdam, 1105 AZ - Amsterdam/NL
  • 2Radiology And Nuclear Medicine, Amsterdam UMC, University of Amsterdam, 1105AZ - Amsterdam/NL
  • 3Epidemiology, Netherlands Comprehensive Cancer Organization (IKNL), 5612HZ - Eindhoven/NL
  • 4Pathology, Amsterdam UMC, University of Amsterdam, 1105 AZ - Amsterdam/NL
  • 5Medical Oncology, Catharina Hospital Eindhoven, 5602 ZA - Eindhoven/NL
  • 6Radiotherapy, Catharina Hospital, 5623EJ - Eindhoven/NL
  • 7Medical Oncology, ETZ Elisabeth Hospital, 5022 GC - Tilburg/NL
  • 8Surgery, Elisabeth-TweeSteden Hospital, 5022GC - Tilburg/NL
  • 9Medical Oncology, Sint Antonius Hospital, 3435CM - Nieuwegein/NL
  • 10Medical Oncology, Leids Universitair Medisch Centrum (LUMC), 2333 ZA - Leiden/NL
  • 11Gi Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 12Medical Oncology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 13Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ - Amsterdam/NL
  • 14Radiotherapy, Amsterdam UMC, University of Amsterdam, 1105 AZ - Amsterdam/NL

Abstract

Background

Preliminary data from the TRAP study demonstrated feasibility of neoadjuvant chemoradiation (nCRT) with trastuzumab and pertuzumab. Here, we present updated survival results with propensity score matching, including potential predictive biomarkers for response to this treatment.

Methods

Patients (pts) with HER2+ resectable esophageal adenocarcinoma (EAC) received nCRT with trastuzumab and pertuzumab (Schokker et al, JCO 2018 suppl. 4057). Survival data was compared with patients not receiving study medication in the Dutch Cancer Registry, using propensity score matching (1:4) based on a logistical regression model, matching for baseline demographic and clinical characteristics. HER2 status was not included as a matching variable, since it was unknown in the majority of pts in the matched cohort. Associations between baseline F-FDG uptake on PET scans, measured by the maximum standardized uptake value (SUVmax), or ΔSUVmax and pathological complete response (pCR) were assessed. Furthermore, expression of HER2 and growth factor receptor-bound protein (Grb)7 was assessed by immunohistochemistry on baseline biopsies. Results were correlated with pCR and survival.

Results

40 pts were enrolled and pCR was seen in 34%. Progression-free survival (PFS) rates at 1 and 3 years were 83% and 72%, respectively, with 1- and 3-year overall survival (OS) rates of 90% and 71% (median follow-up 32.1 months). A statistically significant difference in OS was observed for nCRT with trastuzumab and pertuzumab compared to nCRT (3-year OS rate 71% vs 54%, p = 0.039). Baseline and post-treatment PET scans were available for 40 and 34 pts, respectively. Baseline SUVmax was not predictive for recurrence or death, neither did ΔSUVmax correlate with pCR (p > 0.05). HER2 3+ pts and pts with Grb7+ tumours at baseline demonstrated a significantly better response to treatment (p = 0.016 respectively p = 0.007).

Conclusions

Compared to a propensity score matched cohort receiving nCRT, OS of pts with resectable HER2+ EAC receiving nCRT with trastuzumab and pertuzumab is statistically better. Grb7 and HER2 3+ are potential predictive biomarkers for response to this treatment.

Clinical trial identification

NCT02120911 April 23, 2014.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Roche.

Disclosure

R.H.A. Verhoeven: Research grant / Funding (self): Roche; Research grant / Funding (self): Bristol-Myers Squibb. M. van Oijen: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nordic. G.A.P. Hospers: Advisory / Consultancy, Payment to institution: Amgen; Advisory / Consultancy, Payment to institution: Roche; Advisory / Consultancy, Payment to institution: MSD; Advisory / Consultancy, Research grant / Funding (institution), Payment to institution: BMS; Advisory / Consultancy, Payment to institution: Pfizer; Advisory / Consultancy, Payment to institution: Novartis; Research grant / Funding (institution), Payment to institution: Seerave. M. Bijlsma: Research grant / Funding (institution): Celgene; Advisory / Consultancy: Servier. M.I. van Berge Henegouwen: Honoraria (institution), Research grant / Funding (institution): Stryker; Honoraria (institution), Research grant / Funding (institution): Olympus; Honoraria (institution), Advisory / Consultancy: Medtronic; Honoraria (institution), Research grant / Funding (institution): Mylan. H.W.M. van Laarhoven: Honoraria (self), Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy, Research grant / Funding (institution): Nordic Group; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Bayer Schering Pharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Philips Healthcare; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.