SAKK Lung Cancer Group Current activities and future projects
SAKK Lung Cancer Group Open group of physicians interested in lung cancer Mostly Medical Oncologists, but also Thoracic Surgeons Radiation oncologists Pathologists Pneumologist Meet 4x/year
NSCLC Stages Ib-II Participation in IALT and Notch trial Bad recruitement Participation in EORTC trial Adjuvant Chemotherapy +/- Bevacizumab
Overview Stage IIIA -> SAKK 16/00 Stage IIIB -> SAKK 16/01 Stage IV -> SAKK 19/05 Mesothelioma -> SAKK 17/04 Translational research -> all
Stage III, how it started SAKK 16/96
Results of SAKK 16/96 Study: 3 x Cisplatin/Taxotere neoadjuvant (Betticher, JCO 2003) Overall Survival (ITT population, n=90) Overall survival 1.8 complete resection.6.4 all.2 0 p<0.0001 incomplete resection 0 10 20 30 40 50 60 Months
SAKK 16/00 Hypothesis: Neoadjuvant RT increases complete resection rate -> EFS Chemotherapy: SAKK 16/00 TRIAL DESIGN Cisplatin 100 mg/m 2 d1 Docetaxel 85 mg/m 2 d1 Radiotherapy: Randomization Arm A Arm B Chemotherapy Chemotherapy Radiotherapy Surgery Surgery 3 weeks after last chemotherapy 44 Gy in 22 fractions concomitant boost in 3 weeks, Surgery 3-4 weeks after termination of radiotherapy
SAKK 16/00 Preliminary pooled data on 47 patients RR (CT) % operable % CR PR 2.1 51.0 no 14.9 NC PD 29.8 8.5 yes 72.3 NA unknown 2.1 6.4 Information missing 12.8 No perioperative deaths!
RTOG study, activated 05/05 accrual 5, planned 574
N3
SAKK 16/01 - Hypothesis: IIIB trimodality therapy with neoadjuvant RT Staging / Mediastinocopy Chemotherapy Cycle 1 Cycle2 Cycle 3 RT 44 Gy 21 d 14-28 d 21-28 d Surgery Chemotherapy: Docetaxel 85 mg/m2 Cisplatin 100 mg/m2 Accelerated concomitant boost 22 x 2 Gy in 3 weeks (7 fx/week) R. Stupp
Preliminary results: EFS (n = 20/46) Figure 1: SAKK 16/01 event-free survival (primary endpoint) 0.0 0.2 0.4 0.6 0.8 1.0 / // / / / / 0 4 8 12 16 20 24 Event-free survival (months)
Study Design: Pilot 16/07 NSCLC IIIB T4, N0-N2 N3, Organ infitration* Pl. or per. effusion S o r a f e n i b RT 44 Gy yes Chemotx x 4 cy Response no RT- Chemo 60 Gy Chemotx x 4 cy Like stage IV disease Surgery S. Peters * Aorta, Esophagus, myocardium
Stage IV, a new paradigm: Experimental first line therapy? Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small cell lung cancer (NSCLC) preliminary results of SAKK 19/03 Giannicola D'Addario Registration Gefitinib 250 mg/day until progression Gemcitabine 1250 mg/m 2 d1 and d8 Cisplatin 80 mg/m 2 d1 every 3 weeks for up to 6 cycles Follow-up
Response to gefitinib ( n = 63 ) Week CR PR SD PD NA* DSR % ORR% 6 0 4 29 21 9 52.3 6.3 10-12 1 5 17 36 4 36.5 9.5 18 0 5 8 39 11 20.6 7.9 Response to chemotherapy ( n = 23 ) CR PR SD PD NA DSR % ORR % 0 9 9 4 1 78.2 39.1 Median overall survival was 42.7 weeks (10.0 months)
Stage IV: SAKK 19/05 - Hypothesis: First line combined targeted therapy in NSCLC? Registration Erlotinib 150 mg/day + Bevacizumab 15 mg/kg q3w until progression Gemcitabine 1250 mg/m 2 d1 and d8 plus Cisplatin 80 mg/m 2 d1 or Carboplatin AUC 5 every 3 weeks for up to 6 cycles Follow-up For stage IIIB/IV non-squamous NSCLC No cavitation, CNS metatastases, anticoagulation Not requiring immediate chemotherapy F. Zappa
SAKK 17/00 R. Stahel et SAKK 61 pts 58 operated 1 postoperative death 1 year OS 67%
Multicenter randomized phase II trial (SAKK 17/04) Q3 2005 Part 1 Part 2 Registration after staging Chemotherapy * Restaging Surgery Follow-up if not operable Reassessment R0 or R1 R2 Follow-up Randomisation Arm A: No Radiotherapy Arm B: Hemithoracic Radiotherapy *3 cyles of cisplatin/pemetrexed R. Stahel
A randomised, multi centre Phase II trial of ZD6474 vs Vinorelbine in patients with relapsed mesothelioma (T. Rordorf) Primary endpoint: clinical benefit (CB=CR+PR+SD) CB<30% not worth further investigation; CB>45% promissing Total number of patients needed: 65 stage I analysis after 46 patients Inoperable or relapsed MPM after First line treatment (N=65) Zactima 300 mg po Stage I Analysis (46 pts) Zactima 300 mg po Navelbine 30 mg/m2 iv weekly Navelbine 30 mg/m2 iv weekly
Gene expression in blood discriminates patients with lung cancer from healthy volunteers M. Brutsche et al., Barcelona 2005 BLOOD Normal (n=20) SCLC (n=10) NSCLC (n=8)
planned trials Stage IV SAKK 19/08??? SCLC In planning: phase II trial with targeted agent
Please come!