1. NSCLC stage IIIA type of chemotherapy ? Swiss tumor board Bern – 26.3.2009 Dr. Christian Monnerat Département Pluridisciplaire d’Oncologie – Hôpital Neuchâtelois Service de génétique médicale – CHUV - Lausanne

2. NSCLC stage IIIA (treated in 2004) Summary of the case presented by Dr. Morand NSCLC cT2 cN1 cM0 = minimal stage IIB, possibly IIIA (no mediastinoscopy)  68 y. old, liver comorbidities, restrictive and obstructive pneumopathy  Cytology : squamous cancer (G2 ?) obtained by bronchoscopy  CT: 5 cm mass (left sup lobe) and bi-hilar ADP, liver ? (5 mm)  PET-CT: no distant metastases, ADN near pulmonary vein (N1 ?) Tumor resectable ? - yes  Patient operable ? - yes

3. NSCLC stage IIIA Neoadjuvant chemotherapy - indications http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf  Neoadjuvant treatment only in N2 stages  Chemotherapy  Chemoradiation

4. NSCLC stage IIIA Neoadjuvant chemotherapy - indications http://www.esmo.org/education/esmo-clinical-recommendations.html Preoperative cisplatin-based combination chemotherapy can be considered in patients with stage IIIA N2 disease [II, B]. No pre-operative chemoradiation in Europe - SAKK protocoll ?

5. NSCLC stage IIIA Neoadjuvant chemotherapy Robinson - CHEST 2007; 132:243S–265S t using neoadjuvant therapy followed by surgery for known stage IIIA lung cancer as a routine therapeutic option is not supported by current published randomized trials Combination chemoradiotherapy, especially delivered concurrently, is still the referred treatment…

6. NSCLC stage IIIA Neoadjuvant chemotherapy – the pIII trials Robinson - CHEST 2007; 132:243S–265S t no consistent surgical (pathologic) staging Variable numbers of much better prognosis or poorer prognosis patients small numbers of patients because of poor accrual

7. NSCLC stage IIIA Neoadjuvant chemotherapy – the SAKK trial Betticher - J Clin Oncol 2002 ; 21:1752-1759. Clearance of N2 disease is a good prognostic factor for survival 90 patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC 3 cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 d1-2 ORR of 66% median dose-intensity 84.7 mg/m2 for docetaxel 94.6 mg/m2 for cisplatin.

8. NSCLC stage IIIA (treated in 2004) Summary of the case presented by Dr. Morand NSCLC cT2 cN1 cM0 = minimal stage IIB, possibly IIIA (no mediastinoscopy)  68 y. old, liver comorbidities, restrictive and obstructive pneumopathy  Cytology : squamous cancer (G2 ?) obtained by bronchoscopy  CT: 5 cm mass (left sup lobe) and bi-hilar ADP, liver ? (5 mm)  PET-CT: no distant metastases, ADN near pulmonary vein (N1 ?) Due to comorbidities (and age ?), no neoadjuvant chemotherapy have the « chance » to escape from chemotherapy

9. NSCLC stage IIIA (treated in 2004) Summary of the case presented by Dr. Morand NSCLC pT2pN2(6/36), cM0 = stage IIIa  3.5.04 resection of left upper lobe and of apical segment of inferior lobe, arterial sleeve resection, central lymph node dissection  pT2pN2(6/36), G2, extralymphatic spread of cancer, close to resection margin (R0?)  Six cycles of weekly paclitaxel-carboplatin Higher pathologic stage than clinically expected  Recommandation of adjuvant chemotherapy

10. NSCLC stage IIIA Adjuvant chemotherapy – meta-analysis Pignon – LACE metaanalysis - J Clin Oncol 2008; 26:3552-3559 Cisplatin : OS-HR = 0.89 - DFS-HR = 0.84  NCCN, ESMO and AACP do agree on adjuvant chemotherapy

11. NSCLC stage IIIA Adjuvant chemotherapy Less toxic regimens are needed …(or « better » patients ) A persistent problem with postoperative chemotherapy has been administering the planned doses and cycles of chemotherapy Unfortunately, the experience of ongoing trials shows that the problem has not resolved and only approximately 65% of the planned dose of chemotherapy is actually received. Patient is doing well after 4 years  Have the 6 weekly paclitaxel carboplatin chemotherapy made the difference ? Robinson - CHEST 2007; 132:243S–265S