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What to do in stage III non small-cell lung cancer?

What to do in stage III non small-cell lung cancer?. Miklos Pless 28. November 2013. CRT: Concomitant vs. Sequential Meta-Analysis 2010 (HR 0.84, Cochrane 0.74). Auperin, JCO 2010. CRT: Chemotherapy type not so important? CALGB 9431 (phase II). Vokes, JCO 2007.

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What to do in stage III non small-cell lung cancer?

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  1. What to do in stage III non small-cell lung cancer? Miklos Pless 28. November 2013

  2. CRT: Concomitant vs. SequentialMeta-Analysis 2010 (HR 0.84, Cochrane 0.74) Auperin, JCO 2010

  3. CRT: Chemotherapy type not so important?CALGB 9431 (phase II) Vokes, JCO 2007

  4. CRT: Role of induction chemotherapyCALGB 39801 Vokes, JCO 2007

  5. CRT: role of consolidation CT after CRT? 45 trials, 9 phase III, 36 phase II with 51 arms No difference between the two groups, med OS: CT 18.5 mo vs no CT 18.1 mo Yamamoto S. et al., J. Clin. Oncol. 30, 2012, suppl. Abstr.7000

  6. CRT: role of hyperfractionationRTOG 9410 Arm 3: 70 Gy: 1.2 Gy 2x/d Arm 2: 63 Gy: 1.8 Gy/d HR 0.925 Curran, JNCI 2011

  7. CRT: Role of high doses of RTRTOG 0617 Bradley , ASCO 2013

  8. Operable stage IIIA:Adjuvant Chemotherapy: OS better! Winton, NEJM 2005

  9. Operable Stage IIIADoes adjuvant RT help? NO! PORT Cochrane, 2010

  10. JNCI, 2007 • Unresectable (?) N2 • With response to Induction 3 x Cis/Carbo + X • OP vs. RT (60 Gy) • 1. EP: OS • 50% complete resection! • 41% downstaging to ≤ypN1

  11. Lancet 2009 • Resectable N2 • Induction CRT: 3x Cis/Eto + RT 45 Gy • If no PD: RT to 61Gy vs. OP • 1. EP: OS OS PFS

  12. Overall Survival (ITT population, n=90) Overall survival 1 .8 complete resection .6 .4 .2 0 0 10 20 30 40 50 60 incomplete resection Months p<0.0001 The activity of the SAKK groupSAKK 16/96 (Phase II) 3 x Cisplatin/Taxotere neoadjuvant (Betticher, JCO 2003) all

  13. Is trimodal better than bimodal?SAKK 16/00 Stratification factors: Mediastinal bulk (≥5cm vs. <5cm), weight loss (≥5% vs. <5% in past 6 months), center Chemotherapy 3-4 weeks Radiotherapy Surgery 3 weeks Arm A: RT 44 Gy in 22 fractions in 3 weeks Accelerated conc. boost * * CDDP 100mg/m2 d1 x 3 cy q3w DXT 85mg/m2 d1 x 3 cy q3w +G-CSF Randomization Arm B: no RT Surgery Chemotherapy 3-4 weeks * * Staging: (PET-) CT: PD went off study Presented by: Miklos Pless

  14. Overall Survival Pless ASCO 2013

  15. Stage III • Very heterogeneous disease • <30% can be cured (70-80% are NOT!) • Both local and distant relapse are a problem! • Requires bimodal treatment • always Chemotherapy: minor effect • Surgery vs. Radiotherapy? • Trimodal treatment?

  16. Summary & Conclusions Which Chemotherapy?(Cis-)Platinum based, concurrent type and dose Which Radiotherapy?>60 Gy, less than 70 Gy type, dose, fraction Which combination? Surgery + Chemotherapy Stage IIIA/N2 Radiotherapy + Chemotherapy Stage IIIB/IIIA? all three? Probably not

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