X Mignard1, M Antoine2, D Moro-Sibilot3, C Dayen4, B Mennecier5, R Gervais6, E Amour7, B Milleron7, F Morin7, G Zalcman8, M Wislez9. 1. Sorbonne Université, GRC n(o) 04, Theranoscan, 75252 Paris, France. 2. Sorbonne Université, GRC n(o) 04, Theranoscan, 75252 Paris, France; AP-HP, Groupe Hospitalier HUEP, Hôpital Tenon, service de cytologie et anatomie pathologique, 75970 Paris, France. 3. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; Unité d'oncologie thoracique-pneumologie, CHU de Grenoble, 38700 La Tronche, France. 4. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; Service de pneumologie, maladies infectieuses et tropicales, centre hospitalier de Saint-Quentin, BP 608, 02321 Saint-Quentin cedex, France. 5. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; Service de pneumologie, CHU de Strasbourg, 67000, Strasbourg, France. 6. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; Centre François-Baclesse, 14000 Caen, France. 7. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France. 8. Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; Service d'oncologie thoracique, hôpital Bichat-Claude-Bernard, AP-HP, 75018, Paris, France. 9. Sorbonne Université, GRC n(o) 04, Theranoscan, 75252 Paris, France; Intergroupe francophone de cancérologie thoracique (IFCT), 10, rue de la Grange-Batelière, 75009 Paris, France; AP-HP, Groupe hospitalier HUEP, hôpital Tenon, ervice de pneumologie, 75970 Paris, France. Electronic address: marie.wislez@aphp.fr.
Abstract
BACKGROUND: Programmed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC). METHODS: This phase II study is designed to administrate three durvalumab IV infusions (10mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (>4cm) or stage II, ≥18 years of age, WHO performans status 0-1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection<85% (P0) is considered unacceptable. P1 hypothesis is of 95%, and with a study power of 90% and an alpha risk of 5% (two-steps Fleming's procedure), 81 patients are required. EXPECTED RESULTS: To establish whether neoadjuvant immunotherapy is feasible and could improve the survival of patients with early-stage NSCLC.
BACKGROUND:Programmed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC). METHODS: This phase II study is designed to administrate three durvalumab IV infusions (10mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (>4cm) or stage II, ≥18 years of age, WHO performans status 0-1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection<85% (P0) is considered unacceptable. P1 hypothesis is of 95%, and with a study power of 90% and an alpha risk of 5% (two-steps Fleming's procedure), 81 patients are required. EXPECTED RESULTS: To establish whether neoadjuvant immunotherapy is feasible and could improve the survival of patients with early-stage NSCLC.
Authors: Elizabeth Ahern; Ben J Solomon; Rina Hui; Nick Pavlakis; Ken O'Byrne; Brett G M Hughes Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751
Authors: Pranshu Mohindra; Amit Sawant; Robert J Griffin; Narottam Lamichhane; Erina Vlashi; Meng Xu-Welliver; Michael Dominello; Michael C Joiner; Jay Burmeister Journal: J Appl Clin Med Phys Date: 2019-02-22 Impact factor: 2.102