Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): Outcomes update of North American Intergroup 0139 (RTOG 9309)

7014 Background: Surgery after CT/RT remains controversial for patients (pts) with stage IIIA(pN2) NSCLC. Initial analyses of INT 0139 showed significantly better progression-free survival (PFS), but not overall survival (OS), in the trimodality arm. (PASCO 2003) With longer follow-up (≥2.5 yrs per pt), new analyses of primary endpoints PFS and OS were conducted. Methods: Pts with PS 0–1 and T1–3, pN2, M0 NSCLC were randomized if resection was technically feasible. All received cisplatin 50 mg/m2 d1, 8, 29, 36 and etoposide 50 mg/m2 d1–5, d29–33 (PE) and RT to 45 Gy starting day 1. Arm 1 had resection if no progression (PD), then PE X2; Arm 2 completed RT to 61 Gy with PE X2. Intent to treat analyses used Kaplan-Meier estimates, log-rank tests and Cox multivariate models; exploratory analyses used logistic regression. All CI are 95% and p-values, 2-sided. Results: 396 eligible pts were enrolled (Arm 1, 202; Arm 2, 194; well-balanced on all factors). Treatment-related deaths: Arm 1, 16 (7.9%), of which 10 (5.0%) were within 30 days postop; Arm 2, 4 (2.1%). Deaths by type of surgery: 5/23 (22%) simple and 9/31 (29%) complex pneumonectomies, 1/98 (1%) lobectomies. Arm 1 pathology (n=164): T0N0, 29 (18%); TanyN0, 76 (46%). Arm 1 PFS is superior: median 12.8 vs 10.5 mos, p=0.017, HR 0.77 (0.62, 0.96); 5-yr 22.4% vs 11.1%. More pts on Arm 1 are alive without PD (p=0.008), but more died without PD (p=0.021). OS curves overlap for 2 yrs, but separate late favoring Arm 1: median 23.6 vs 22.2 mos, p=0.24, HR 0.87 (0.70,1.10); 5-yr 27.2% vs 20.3%, odds ratio for 5-yr survival 0.63 (0.36, 1.10, p=0.10). 96 pts are alive/censored. Independent favorable OS predictors: female, no weight loss. Arm 1 5-yr OS if pN0 at surgery was 41%; pN1–3, 24%; no surgery, 8% (p< 0.0001). Conclusions: 1) Longer follow-up of INT 0139 confirms significantly improved PFS but not OS when surgery follows CT/RT in pts with stage IIIA(pN2) NSCLC, 2) there is a trend for better 5-yr OS with trimodality therapy, 3) pN0 at surgery predicts long-term survival, 4) surgery after CT/RT can be considered in fit pts, 4) this approach may not be optimal if a pneumonectomy is needed. No significant financial relationships to disclose.