TY - JOUR
T1 - Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma
T2 - A Single Arm Phase II Feasibility Trial (PERFECT)
AU - van den Ende, Tom
AU - Clercq, Nicolien de
AU - van Berge Henegouwen, Mark I
AU - Gisbertz, Suzanne S
AU - Geijsen, Debby
AU - Verhoeven, Rob
AU - Meijer, Sybren L
AU - Schokker, Sandor
AU - Dings, Mark
AU - Bergman, Jacques J G H M
AU - Haj Mohammad, Nadia
AU - Ruurda, Jelle P
AU - van Hillegersberg, Richard
AU - Mook, Stella
AU - Nieuwdorp, Max
AU - de Gruijl, Tanja D
AU - Soeratram, Tanya T D
AU - Ylstra, Bauke
AU - van Grieken, Nicole C T
AU - Bijlsma, Maarten F
AU - Hulshof, Maarten C C M
AU - van Laarhoven, Hanneke W
N1 - Funding Information:
T. van den Ende reported the PERFECT trial was funded by Hoffmann-La Roche Ltd., Basel, Switzerland. M.I. van Berge Henegouwen reported other from Mylan, Alesi surgical, Johnson & Johnson, and Medtronic; grants from Olympus and Stryker outside the submitted work. R.H.A. Verhoeven reported grants from Roche and Bristol Myers Squibb outside the submitted work. N. Haj Mohammad reported other from Eli Lilly, Servier, MSD, BMS, and AstraZeneca outside the submitted work. T.D. de Gruijl reported other from Hoffmann-La Roche Ltd during the conduct of the study; grants from Idera Pharmaceuticals; other from DCPrime BV, Macrophage Pharma, and LAVA Therapeutics outside the submitted work. M.F. Bijlsma reported grants from Celgene and personal fees from Servier outside the submitted work. H.W.M. van Laarhoven reported grants and nonfinancial support from Roche, Celgene, and Janssen and grants from Dutch Cancer Society during the conduct of the study; grants and nonfinancial support from Bayer, Philips, and Roche; grants and personal fees from BMS; grants, personal fees, and nonfinancial support from Lilly, Nordic, Servier, and Merck; personal fees from MSD outside the submitted work. No disclosures were reported by the other authors.
Funding Information:
We acknowledge the help provided by G.K.J. Hooijer for cutting and staining the IHC slides. We also thank the participants of the PERFECT trial and all supporting staff in the Amsterdam UMC and UMC Utrecht. This work was funded by Hoffmann-La Roche Ltd., Basel, Switzerland.
Funding Information:
We acknowledge the help provided by G.K.J. Hooijer for cutting and staining the IHC slides. We also thank the participants of the PERFECT trial and all supporting staff in the AmsterdamUMCandUMCUtrecht. This workwas funded byHoffmann- La Roche Ltd., Basel, Switzerland.
Publisher Copyright:
© 2021 American Association for Cancer Research.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Purpose: The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of nCRT combined with programmeddeath ligand-1 (PD-L1) inhibition for rEAC. Patients and Methods: Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1, 200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies. Results: We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (n = 4), patient choice (n = 2), and death (n = 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNg signature was higher in responders compared with nonresponders (P = 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs. Conclusions: Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.
AB - Purpose: The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of nCRT combined with programmeddeath ligand-1 (PD-L1) inhibition for rEAC. Patients and Methods: Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1, 200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies. Results: We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (n = 4), patient choice (n = 2), and death (n = 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNg signature was higher in responders compared with nonresponders (P = 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs. Conclusions: Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.
UR - http://www.scopus.com/inward/record.url?scp=85106021321&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-4443
DO - 10.1158/1078-0432.CCR-20-4443
M3 - Article
C2 - 33504550
VL - 27
SP - 3351
EP - 3359
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 12
ER -