LBA3_PR – An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement. Primary end-point analysis of Lung ART (IFCT-0503, UK NCRI, SAKK) NCT00410683.
C. Le Pechoux1, N. Pourel2, F. Barlesi3, C. Faivre-Finn4, D. Lerouge5, G. Zalcman6, D. Antoni7, B. Lamezec8, U. Nestle9, P. Boisselier10, F. Thillays11, A. Paumier12, E. Dansin13, K. Peignaux14, J. Madelaine15, E. Pichon16, A. Larrouy17, O. Riesterer18, A. Lavole19, A. Bardet20
1Radiation Oncology, Gustave Roussy, Villejuif, France, 2Radiation Oncology, Institut Sainte Catherine, Avignon, France, 3France and Institut Gustave Roussy, Aix Marseille Université, Aix-Marseille University, CRCM, APHM, Marseille, Villejuif, CEDEX 20, France, 4Clinical Oncology, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK, 5Radiation Oncology, Centre Baclesse, Caen, France, 6Department of Thoracic Oncology and CIC1425, Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université Paris-Diderot, Paris, France, 7Radiation Oncology, Institut de Cancerologie Strasbourg Europe, Strasbourg, France, 8Radiation Oncology, Clinique Armoricaine de Radiologie, St. Brieuc, France, 9Radiation Oncology, Universitätsklinikum Freiburg Klinik für Innere Medizin Hämatologie, Onkologie und Stammzelltransplantation, Freiburg Im Breisgau, Germany, 10Radiation Oncology, ICM Regional Cancer Institute of Montpellier, Montpellier, CEDEX 5, France, 11Radiation Oncology, Institut de Cancérologie de l’ouest,, Saint Herblain, France, 12Radiation Oncology, ICO Site Paul Papin, Angers, France, 13Medical Oncology, Centre Oscar Lambret, Lille, CEDEX, France, 14Radiation Oncology, Centre Georges Francois Leclerc, Dijon, France, 15Medical Oncology, Centre Hospitalier Caen, Caen, France, 16Pneumology, CHRU Bretonneau, Tours, CEDEX 9, France, 17Radiation Oncology, Centre de Cancerologie Paris Nord, Sarcelles, France, 18Radiation Oncology, University Hospital Zurich and Center for Radiation Oncology KSA-KSB, Cantonal Hospital Aurau, Zurich, Switzerland, 19Pneumology, Hopital Tenon, Paris, France, 20Biostatistics, Institut Gustave Roussy, Villejuif, France
Background: Adjuvant PORT has been controversial since publication of a meta-analysis showing PORT could be deleterious especially in pN0 pN1 pts. However, changes have taken place in the management of stage IIIAN2 NSCLC pts including use of adjuvant chemotherapy (CT), patients’ workup, quality of surgery and radiotherapy. Therefore the role of PORT warranted further investigations in high risk pts.
Methods: LungART is a multi-institutional randomized phase III trial comparing mediastinal PORT (54 Gy/27-30 fractions) to no PORT. Pts were eligible if they were PS 0-2, had a complete resection with nodal exploration, proven N2 disease; prior (neo)-adjuvant CT was allowed. The main end-point was disease-free survival (DFS). 500 pts and 292 events were required to show an improvement in DFS from 30% to 42% with PORT (bilateral test). Secondary endpoints included toxicity, local control, patterns of recurrence, overall survival (OS), second cancers, prognostic and predictive factors of treatment effect.
Results: Between August 2007 and July 2018, 501 patients were randomized after surgery or after CT: 252 pts allocated to PORT, and 249 to CA. Median age was 61 (range=36-85), 66% male, histology: mostly adenocarcinoma (73%) and work-up included PET scan in 91% pts. Most patients received CT (post op 77%, pre-op 18%). Analysis for DFS was performed with a median FU of 4.8 yrs; toxicity evaluated on 487 pts (246 in CA). Early and late Gr 3-5 cardio-pulmonary toxicity was respectively 7 and 20% in PORT vs 3,2 and 7,7 % in CA. DFS hazard ratio was 0.85 (95% CI 0.67; 1.07); p=0.16; median DFS was 30.5 months in PORT arm [24;48] and 22.8 in CA [17;37]; 3-year DFS was 47.1% with PORT vs 43.8% with no PORT. 3-year OS was 66.5% with PORT vs 68.5% with no PORT.
Conclusions: LungART is the first European randomized study evaluating modern PORT after complete resection, in pts selected predominantly with PET scan and having received (neo)adjuvant CT. 3-year DFS was higher than expected in both arms and PORT was associated with a non-statistically significant 15% increase in DFS among stage IIIAN2 pts.
Clinical trial identification: NCT00410683
Legal entity responsible for the study: Gustave Roussy
Funding: French National Cancer Institute (INCa), French Health Ministry (PHRC), Gustave Roussy and CRUK grant (A13969).
Disclosure: C. Le Pechoux: Honoraria (institution): Amgen; Honoraria (institution), Advisory/Consultancy: Astra Zeneca; Honoraria (institution): Lilly; Honoraria (self): PrimeOncology; Honoraria (institution): Medscape; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Nanobiotix. F. Barlesi: Honoraria (self), Personal Fees: Astra Zeneca; Honoraria (self): Bayer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Boehringer–Ingelheim; Honoraria (self): Eli Lilly Oncology; Honoraria (self): F. Hoffmann–La Roche Ltd; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer ; Honoraria (self): Takeda. C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding (institution): Astra Zeneca; Research grant/Funding (institution): Elekta. G. Zalcman: Research grant/Funding (institution): Fondation Roche; Honoraria (self), Travel/Accommodation/Expenses: Astra Zeneca; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Inventiva; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Abbvie; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Da Volterra. J. Madelaine: Honoraria (self), Dr JM received support: Astra Zeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD France; Honoraria (self): Roche SAS; Honoraria (self): Actelion; Honoraria (self): GSK; Honoraria (self): Bristol-Myers Squibb. A. Bardet: Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.