1. Multimodality treatment of stage III NSCLC Jan P van Meerbeeck EIS-Geneva

2. Are you « out » when not offering your patient concurrent chemoradiotherapy?

8. Is there an optimal induction regimen? Van Meerbeeck 2007 EORTC 08941 3 cycles platinum-based induction chemotherapy Overall response : 61% Surgical resection Thoracic radiotherapy 60 Gy, 2 Gy/f oid No response Off study

9. response rate (%) in regimens with >= 20 pts *: CR + PR + mR Van Meerbeeck, 2003 23-69 45 20 etoposide-carboplatin 54 30 76 55 23 221 N 26-63 43 docetaxel-cisplatin 43-84 65 vinb-ifosf-cisplatin 45-72 59 vindesin-cisplatin 28-55 41 etoposide-cisplatin 46-69 58 paclitaxel-carboplatin 60-73 67 gemcitabine-cisplatin 95% CI ORR* (%) regimen

11. Which platinum? Ardizzoni, 2006

12. 3 rd generation drugs Vokes, 2002 CALGB 9431 IIIB n= 175 Cis gemcitabine Full dose x2 Cis paclitaxel Full dose x2 Cis vinorelbine Full dose x2 Cis gemcitabine X 2 reduced dose + 66 Gy TRT Cis paclitaxel X2 reduced dose + 66 Gy TRT Cis vinorelbine X2 reduced dose + 66 Gy TRT ORR: 40% (27-55) ORR: 33% (20-48) ORR: 44% (29-60)

14. Which is the better sequence with RT? Consolidation chemotherapy Concurrent chemoradiotherapy Curran, 2001 Fournel, 2005 Induction chemotherapy Concurrent chemoradiotherapy Consolidation chemotherapy Zatloukal, 2004 Concurrent chemoradiotherapy Induction chemotherapy Radiotherapy

18. CALGB 39801 Median survival: 11.4 m 14m (p= 0.15 ) Stage III: N= 366 randomization CT/TRT Weekly paclitaxel 50 mg/m2 Weekly Cb AUC 2 Daily TRT - 66 Gy Induction CT 2 cycles q 3w Paclitaxel 200 mg/m2 Cb AUC 6 CT/TRT Weekly paclitaxel 50 mg/m2 Weekly Cb AUC 2 Daily TRT – 66 Gy Vokes, 2004

19. IFCT Median survival: 11m 14m (p= NS ) Stage III: N= 574 Induction Chemo Cis-vinorelbine x3 Daily TRT - 66 Gy TRT 66 Gy + daily carboplatine 15 mg/m² Gervais, 2005

21. US Oncology Median survival: 27m 16 m (p= 0.07 ) Carter, 2004 Stage III: N= 220 Induction Carboplatin-paclitaxel CT/TRT Weekly paclitaxel 45 mg/m2 Weekly Cb AUC 2 Daily TRT – 66 Gy Observation N= 58 Paclitaxel 3-weekly for 6m N= 61

25. Expected meta-analyses 1199 C -> R vs. cCR 2910 R vs. cCR ? 3839 R vs. C -> R HR N Interventions NSCLC coll, 2007 (IPD)

27. SWOG 0023

30. Treatment plan in stage III week staging PET/ CT Cycle 1 Cycle 2 Cycle 3 Radiotherapy Restaging and RT- planning -X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 -X

31. Multimodality treatment anno 2007 *Brain met’s as first failure site in 15-30% 35+ 30+ 25+ Distant progression* 30+ 25+ 20 Local progression 10 20 30 60 Alive: median 17m 5y 3y 2y 1y % of pts, after diagnosis