Cisplatin / etoposide (PE) followed by twice-daily chemoradiation (hfRT/CT) versus PE alone before surgery in stage III non-small cell lung cancer (NSCLC): A randomized phase III trial of the German Lung Cancer Cooperative Group (GLCCG)

7004 Background: In the neoadjuvant treatment setting of stage III NSCLC the additional impact of hfRT/CT after preoperative CT on resectability and survival is open to conjecture. Methods: In a phase III trial patients pts with stage III NSCLC (invasive mediastinal staging obligatory) were stratified (center; stage, IIIA vs IIIB) and then randomized to (arm A) 3 cycles P 55 mg/m2 (d 1+4) / E 100 mg/m2 (d 1–4), followed by hfRT (45 Gy; 2 x 1.5 Gy/d) with concurrent Carboplatin 100 mg/m2 / Vindesin 3 mg (d 1, 8, 15), then surgery and, if no or R1/2-resection, additional hfRT (24 Gy; 2 x 1.5 Gy/d) versus (arm B) 3 cycles of PE followed by surgery and then RT (1.8 Gy/d) with 54 Gy or, if no or R1/2-resection, 68.4 Gy. The primary (secondary) study endpoint was progression free survival PFS (survival S). With 500 pts. evaluable an improvement of median PFS (S) from 10 to 14 (17 to 23) months mo; 3 y.-rate from 8 to 17 (23 to 34) % could be detected. Results: 558 pts. were randomized (10/95–07/03); 32 (6%) were ineligible. On december 1st, 2003 median follow up was 46 mo with outcome data available for 481 pts. Patient characteristics were well balanced between arm A (245 pts.) and arm B (236 pts): male 82%/83%, female 18%/17%; PS 0 86%/87%; PS 1 14%/13%; age 59/59 ys. median; stage IIIA 31%/34%; stage IIIB 69%/66%. Whilst the rate of grade 3/4-esophagitis was significantly different between treatment arms (15%/4%, p < 0.001), there was no significant difference for the response rate after induction (52%/47%; p = 0.35), the proportion of patients with complete tumor resection (111/245, 45% /118/236, 50%; p = 0.30), the treatment related mortality rate (5,6%/5,3%), nor for PFS (median, 10/10 mo; 3 y.-rate, 17%/18%; p = 0.37, log-rank) or S (median, 15/17 mo; 3 y.-rate, 24%/23%; p = 0.89, log-rank). Conclusions: In this trial the addition of hfRT/CT to PE prior to planned surgery had no impact on PFS or S but contributed to significantly higher rates of grade 3/4 esophagitis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly