207_Combined course Presentations

Radiotherapypluschemotherapywithorwithout surgical resectionfor stageIII non-small-cell lungcancer:aphaseIII randomisedcontrolledtrial

KathySAlbain,RSuzanneSwann, ValerieWRusch,AndrewTTurrisi III,FrancesAShepherd, ColumSmith,YuhchyauChen,Robert BLivingston, RichardHFeins,DavidRGandara,WillardAFry,Gail Darling,DavidHJohnson,MarkRGreen,Robert CMiller,JoanneLey,WillliamTSause,JamesDCox

Role of Induction CT-RT: Lung Intergroup Trial 0139

Summary Background Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapywithpromisingratesof survival. WethereforedidthisphaseIII trial tocompareconcurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection. Methods PatientswithstageT1-3pN2M0 non-small-cell lungcancer wererandomlyassigned ina1:1ratiotoconcurrent induction chemotherapy (two cycles of cisplatin [50 mg/m² on days 1, 8, 29, and 36] and etoposide [50 mg/m² on days 1–5 and 29–33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1underwent resection and those in group 2 continued radiotherapy uninterrupted up to61Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysiswasby intention to treat. Thisstudy isregisteredwith ClinicalT rials.gov, number NCT00002550. Findings 202 patients (median age 59 years, range 31–77) were assigned to group 1 and 194 (61 years, 32–78) to group 2. Median OSwas 23· 6 months (IQR 9· 0–not reached) in group 1versus 22· 2 months (9· 4–52· 7) in group 2 (hazard ratio [HR] 0· 87 [0· 70–1· 10]; p=0· 24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1and 24 (point estimate 20%) in group 2 (odds ratio0· 63 [0· 36–1· 10]; p=0· 10). With N0 statusat thoracotomy, the median OS was 34· 4 months (IQR 15· 7–not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) wasbetter in group1than in group2, median 12· 8months(5· 3–42· 2) vs 10· 5months (4· 8–20· 6), HR 0· 77 [0· 62–0· 96]; p=0· 017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicitiesassociated with chemotherapy plusradiotherapy in group 1(77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deathswere treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versuschemotherapyplusradiotherapy.  Group 1:  Group 2:

Lancet 2009;374:379–86

Published Online July27,2009 DOI:10.1016/S0140- 6736(09)60737-6

 429 Stage IIIA ( pN2 ) patients

See Comment page359

LoyolaUniversityChicago StritchSchool of Medicine, Maywood, IL, USA (Prof KSAlbainMD) ;Radiation TherapyOncologyGroup, Philadelphia, PA, USA (RSSwann PhD, JLeyRN) ; Memorial Sloan-Kettering CancerCenter, NewYork, NY, • Cisplatin + Etoposide x 2 • RT 45 Gy • Surgery • 2 additional CT cycles

USA (Prof VWRuschMD) ; WayneStateUniversity, Detroit, MI, USA (Prof ATTurrisi III MD) ; UniversityHealthNetwork, PrincessMargaret Hospital Site, Toronto, ON, Canada (Prof FAShepherdMD) ; TomBakerCancerCenter, Calgary, AB, Canada (Prof CSmithMD) ;University of RochesterMedical Center, Rochester, NY, USA (Prof YChenMD) ;University of ArizonaCancerCenter,Tucson, AZ, USA (Prof RBLivingstonMD) ; Universityof NorthCarolina, Chapel Hill, NC, USA (Prof RHFeinsMD) ;University of Californiaat DavisCancer Center, Sacramento, CA, USA

• Cisplatin + Et poside x 2 • RT 61 Gy • 2 additional CT cycles

Interpretation Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patientswith stage IIIA(N2) non-small-cell lungcancer .

Funding National Cancer Institute, Canadian Cancer Society, andNational Cancer Instituteof Canada.

(Prof DRGandaraMD) ; EvanstonHospital of

Introduction

survival rates that werehigher than expected. 11–13 However,

Albain KS. et al. Lancet 2009;374