Durvalumab and PET-Directed Chemoradiation in Locally Advanced Esophageal Adenocarcinoma: A Phase Ib/II Study.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
medline:
11
8
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
To determine the safety and efficacy of adding the anti-PD-L1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma. Neoadjuvant induction FOLFOX followed by positron emission tomography (PET) directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is clear benefit now for the addition of immune checkpoint inhibitors both in early and advanced stage disease. Given these results we investigated the safety and efficacy of adding durvalumab to induction FOLFOX and preoperative chemoradiotherapy. Patients with locally advanced resectable esophageal/gastroesophageal junction adenocarcinoma received PET-directed chemoradiation with durvalumab before esophagectomy. Patients who had R0 resections received adjuvant durvalumab 1500 mg every 4 weeks for 6 treatments. The primary endpoint of the study was pathologic complete response. We enrolled 36 patients, 33 of whom completed all preoperative treatment and underwent surgery. Preoperative treatment was well tolerated, with no delays to surgery nor new safety signals. Pathologic complete response was identified in 8 [22% (1-sided 90% lower bound: 13.3%)] patients with major pathologic response in 22 [61% (1-sided 90% lower bound: 50%)] patients. Twelve and 24-month overall survival was 92% and 85%, respectively. The addition of durvalumab to induction FOLFOX and PET-directed chemoradiotherapy before surgery is safe, with a high rate of pathologic response, as well as encouraging survival data.
Sections du résumé
OBJECTIVE
To determine the safety and efficacy of adding the anti-PD-L1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma.
BACKGROUND
Neoadjuvant induction FOLFOX followed by positron emission tomography (PET) directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is clear benefit now for the addition of immune checkpoint inhibitors both in early and advanced stage disease. Given these results we investigated the safety and efficacy of adding durvalumab to induction FOLFOX and preoperative chemoradiotherapy.
METHODS
Patients with locally advanced resectable esophageal/gastroesophageal junction adenocarcinoma received PET-directed chemoradiation with durvalumab before esophagectomy. Patients who had R0 resections received adjuvant durvalumab 1500 mg every 4 weeks for 6 treatments. The primary endpoint of the study was pathologic complete response.
RESULTS
We enrolled 36 patients, 33 of whom completed all preoperative treatment and underwent surgery. Preoperative treatment was well tolerated, with no delays to surgery nor new safety signals. Pathologic complete response was identified in 8 [22% (1-sided 90% lower bound: 13.3%)] patients with major pathologic response in 22 [61% (1-sided 90% lower bound: 50%)] patients. Twelve and 24-month overall survival was 92% and 85%, respectively.
CONCLUSIONS
The addition of durvalumab to induction FOLFOX and PET-directed chemoradiotherapy before surgery is safe, with a high rate of pathologic response, as well as encouraging survival data.
Identifiants
pubmed: 36762546
doi: 10.1097/SLA.0000000000005818
pii: 00000658-202309000-00031
doi:
Substances chimiques
durvalumab
28X28X9OKV
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e511-e518Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
G.Y.K. reports grant and personal fees from Astra Zeneca, Bristol-Myers Squibb, and Merck. AJC. A.J.-C.W. reports grant fees from CivaTech Oncology and personal fees from Nanovi A/S and Simphotek Inc. D.R.J. reports personal fees from Astra Zeneca and Merck. S.B.M. reports personal fees from Natera, Bicara, Novartis, Basilea and Daiichi-Sankyo. P.S.A. reports grant and personal fees from ATARA Biotherapeutics, and personal fees from Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, and OutpaceBio. D.H.I. reports personal fees from Astra Zeneca, Bristol-Myers Squibb, Taiho, Merck, Macrogenics, Amgen, Daiichi-Sankyo, Astellas and Adaptimmune. Y.Y.J. reports research funding from Bayer, Bristol-Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, NCI, RGENIX and personal fees from Amerisource Bergen, Arcus Biosciences, Astra Zeneca, Basilea Pharmaceutica, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline, Imedex, Imugene, Lynx Health, Merck, Merck Serono, Michael J. Hennessy Associates, Paradigm Medical Communications, PeerView Institute, Pfizer, Research to Practice, RGENIX, Seagen, Silverback Therapeutics, Zymeworks Inc. D.M. reports personal fees from Astra Zeneca, Bristol-Myers Squibb, Johnson & Johnson, Merck and Boston Scientific. The remaining authors report no conflicts of interest.
Références
van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–2084.
Goodman KA, Ou FS, Hall NC, et al. Randomized phase II study of PET response-adapted combined modality therapy for esophageal cancer: mature results of the CALGB 80803 (Alliance) Trial. J Clin Oncol. 2021;39:2803–2815.
Bendell JC, Meluch A, Peyton J, et al. A phase II trial of preoperative concurrent chemotherapy/radiation therapy plus bevacizumab/erlotinib in the treatment of localized esophageal cancer. Clin Adv Hematol Oncol. 2012;10:430–437.
Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol. 2018;29:1386–1393.
Safran HP, Winter K, Ilson DH, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2022;23:259–269.
Kelly RJ, Lee J, Bang YJ, et al. Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clin Cancer Res. 2020;26:846–854.
Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191–1203.
Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398:27–40.
Janjigian YY, Maron SB, Chatila WK, et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020;21:821–831.
Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251–264.
Niu B, Ye K, Zhang Q, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics. 2014;30:1015–1016.
Chakravarty D, Gao J, Phillips SM, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017;2017.
Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic signaling pathways in the cancer genome Atlas. Cell. 2018;173:321–337e10.
Leichman LP, Goldman BH, Bohanes PO, et al. S0356: a phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. J Clin Oncol. 2011;29:4555–4560.
Ku GY, Kriplani A, Janjigian YY, et al. Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma. Cancer. 2016;122:2083–2090.
Carr RA, Hsu M, Harrington CA, et al. Induction FOLFOX and PET-directed chemoradiation for locally advanced esophageal adenocarcinoma. Ann Surg. 2023;277:e538–e544.
Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018;4:e180013.
Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–2471.
Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–931.
Stamell EF, Wolchok JD, Gnjatic S, et al. The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Oncol Biol Phys. 2013;85:293–295.
Sihag S, Ku GY, Tan KS, et al. Safety and feasibility of esophagectomy following combined immunotherapy and chemoradiotherapy for esophageal cancer. J Thorac Cardiovasc Surg. 2021;161:836–843.e1.
Sihag S, Nobel T, Hsu M, et al. Survival following trimodality therapy in patients with locally advanced esophagogastric adenocarcinoma: does only a complete pathologic response matter? Ann Surg. 2022;276:1017–1022.
Shitara K, Özgüroğlu M, Bang YJ, et al. Molecular determinants of clinical outcomes with pembrolizumab versus paclitaxel in a randomized, open-label, phase III trial in patients with gastroesophageal adenocarcinoma. Ann Oncol. 2021;32:1127–1136.
Meignan M, Sasanelli M, Casasnovas RO, et al. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients. Eur J Nucl Med Mol Imaging. 2014;41:1113–1122.
Erdi YE, Mawlawi O, Larson SM, et al. Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer. 1997;80(suppl):2505–2509.
van den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT). Clin Cancer Res. 2021;27:3351–3359.
Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16:1090–1098.