Hospital Quironsalud, Valencia, Spain
Carlos Fernandez-Martos , Isidro Machado , Carles Pericay , Nuria Salas , Jaime Feliu Batlle , Sanne ten Hoorn , Louis Vermeulen , Ferran Losa , Rocio Garcia Carbonero , Vicente Alonso , Ruth Vera , Javier Gallego , Jaume Capdevila , Antonieta Salud , Miguel Nogué , Joan Maurel , Laura Layos , Clara Montagut , Xabier Garcia-Albeniz
Background: Neoadjuvant chemotherapy (CT) followed by CRT and TME is a treatment option for clinically staged HRRC. The goal of the GEMCAD 1402 trial was to evaluate the benefit of adding an antiangiogenic drug to the neoadjuvant CT. The analysis of primary endpoint showed a better response rate in the experimental arm (Fernandez-Martos et al. Jama Oncol 2019). Here we present 3-year disease-free survival (DFS) and a retrospective analysis of consensus molecular subtypes by Immunohistochemistry (CMSs-IHQ). Methods: Patients (p) with middle or distal third, mrT3/T4/N2 rectal adenocarcinoma were randomly assigned (2:1), to mFOLFOX6 with (arm 1, n=115) or without Aflibercept (arm 2, n=65) prior to CRT (capecitabine with 50.4 Gy in 28 fractions) and TME. Tissue microarrays from 90 (58 arm1, 32 arm 2) p were stained for nine markers (CDX2, FRMD6, HTR2B, ZEB1, KER, MSH2, MSH6, PMS2 and MLH1) by IHQ using both semiquantitative and quantitative approaches. Cases were classified as CMS1-IHQ1, CMS-IHQ2/3 or CMS-IHQ 4 (immune, epithelial or mesenchymal subtypes). Results: In the intention-to-treat population after a median follow-up time of 38 months, 29 p (25%) in arm 1 had a DFS-related event, as compared with 14 p (21%) in arm 2 (HR 1.2063, 95% confidence interval 0.6374 to 2.2829, P=0.5644. The rate of DFS at three years was 75.2% (95% confidence interval, 66.1% to 82.2%) in arm 1 and 81.5% (95% confidence interval, 69.8% to 89.1%) in arm 2 (P=0.5638 by the exact stratified log-rank test). Overall 0/80/10 p were classified as CMS-IHQ1, CMS-IHQ2/3 or CMS-IHQ4 respectively. The pathological complete response (pCR) rate (ypT0N0) was achieved in 27.5% and 0% in epithelial and mesenchymal subtypes respectively. A trend towards worse survival for the mesenchymal subtype was observed. Conclusions: Adding aflibercept to induction mFOLFOX6 is not associated with an improvement in DFS. Our findings suggest that CMSs-IHQ subtypes could be predictive for pCR with this treatment strategy. Clinical trial information: NCT02340949.
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Abstract Disclosures
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Valentina Burgio
2018 ASCO Annual Meeting
First Author: Carlos Fernandez-Martos
2015 ASCO Annual Meeting
First Author: Carlos Fernandez-Martos
2023 ASCO Gastrointestinal Cancers Symposium
First Author: Sigurdis Haraldsdottir