The association of histopathologic features after neoadjuvant chemo-immunotherapy with clinical outcome: Sub-analyses from the randomized double-blinded, placebo-controlled, Phase III IMagyn050/GOG3015/ENGOT-ov39 study.

Autor: Mhawech-Fauceglia P; Sonic health care, Las Vegas, NV, United States., McCarthy D; Pathology Consultants (PC), Springfield, OR, United States., Tonooka A; Division of Pathology at the Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Scambia G; Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del S. Cuore, Rome, Italy., Garcia Y; Parc Tauli Hospital Universitari, Institut d'Investigació I Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain., Dundr P; First Medical Faculty Charles University, General University Hospital in Prague, Prague, Czech Republic., Mills AM; University of Virginia, Charlottesville, VA, United States., Moore K; Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States., Sanada S; Kurume University School of Medicine, Kurume, Japan., Bradford L; Maine Health, Scarborough, ME, United States., Stella GC; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Bookman M; Kaiser Permanente, San Francisco, CA, United States., Sharma SK; University of Chicago Medicine Advent Health, Hinsdale, IL, United States., Selle F; Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France., Molinero L; Genentech, Inc., South San Francisco, CA, United States., He Y; Parexel, Chengdu, China., Khor V; Genentech, Inc., South San Francisco, CA, United States., Landen C; University of Virginia, Charlottesville, VA, United States., Lin YG; Genentech, Inc., South San Francisco, CA, United States. Electronic address: LIN-LIU.YVONNE@gene.com.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Jul; Vol. 186, pp. 17-25. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1016/j.ygyno.2024.03.022
Abstrakt: Objective: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes.
Methods: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes.
Results: The predefined population had 243 evaluable NACT patients, with 48.1% tumors being PD-L1-positive. No statistically significant differences in PFS (16.9 months vs. 19.2 months, p = 0.21) or OS (41.5 months vs. 45.1 months, p = 0.67) between treatment arms were seen. Substantial residual tumor (RT) (3+) was identified in 26% atezolizumab vs. 24% placebo arms (p = 0.94). Most showed no (1+) necrosis (82% vs. 96%, respectively, p = 0.69), moderate (2+) to severe (3+) fibrosis (71% vs. 75%, respectively, p = 0.82), and extensive (2+) inflammation (53% vs. 47% respectively, p = 0.48). No significant histopathologic differences were identified by tissue site or by arm. Multivariate analyses showed increased risk for progression with moderate and substantial RT (13.6 mon vs. 21.1 mon, hazard ratio 2.0, p < 0.01; 13.6 mon vs. 21.1 mon, HR 1.9, p < 0.01, respectively); but decreased risk for death with extensive inflammation (46.9 mon vs. 36.3 mon, HR 0.65, p = 0.02). Inflammation also correlated with greater likelihood of response to NACT/bevacizumab plus immunotherapy (odds ratio 2.9, p < 0.01). Modeling showed inflammation as a consistent but modest predictor for OS.
Conclusions: Detailed histologic assessment of ICS specimens appear to identify characteristics, such as inflammation and residual tumor, that may provide insight to certain clinical outcomes. Future work potentially leveraging emerging tools may provide further insight into outcomes.
Competing Interests: Declaration of competing interest GS reports grant/research support from MSD Italia S.r.l.; consultancy for TESARO Bio Italy S.r.l. and Johnson & Johnson; and speaker bureau/honoraria from Clovis Oncology Italy S.r.l. YG reports fees from advisory boards from GlaxoSmithKline and AstraZeneca; and fees from travel grants and speaker's bureau from Roche, AstraZeneca, MSD, and GlaxoSmithKline. PD reports advisory board honoraria and speaking fees from Novartis, Janssen-Cilag, Amgen, Merck Sharp and Dohme, Roche, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, and Merck. KNM reports research funding from PTC Therapeutics, Lilly, Genentech/Roche, GlaxoSmithKline, Verastem, and Clovis; advisory Board/Consultant role with Aadi, AstraZeneca, Aravive, Alkemeres, Blueprint pharma, Clovis, Caris, Duality, Eisai, EMD Serono, Gilead, GSK, Genentech/Roche, Immunogen, IMab, Janssen, Merck, Mersana, Myriad, Novartis, OncXerna, OncoNova, Panavance, VBL Therapeutics, Verastem, Zentalis, and Tubulis; and Associate Director GOG Partners with GOG Foundation BOD (uncompensated) and ASCO BOD (uncompensated). GCS reports conflicts with AstraZeneca, GlaxoSmithKine, and Clovis. MB reports participation in ad-hoc advisory boards for Genentech-Roche, Merck Sharp & Dohme, AstraZeneca, Clovis Oncology, Seattle Genetics, Aravive, and AbbVie; and consulting fees paid to institution. FS reports honoraria from Astra Zeneca, MSD, Clovis Oncology, Sandoz, and GlaxoSmithKine-Tesaro; consulting or advisory role for AstraZeneca, MSD, and GlaxoSmithKine-Tesaro; speaker's bureau from AstraZeneca, MSD, and GlaxoSmithKline-Tesaro; and travel, accommodation, and/or expenses from AstraZeneca, MSD, GlaxoSmithKline-Tesaro, and Roche. LM reports employment by Genentech and is a stockholder in Roche. YH reports employment by Parexel to provide statistical service for Roche. VK reports employment by Genentech and is a stockholder in Roche. CL reports research funding (institution) from Roche. YGL reports employment by Genentech and is a stockholder in Roche. PM-F reports consulting fees for Genentech-Roche. DM, AT, AMM, SS, LB and SKS report no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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