Do we know how to choose the <br />best maintenance treatment?<br />oliver.gautschi@onkologie.ch<br />
Firstline therapy (metastatic disease)<br />Continuation maintenance<br />Switch maintenance<br />Secondline therapy (at p...
Delay tumor progression<br />Prolong survival<br />Optimal tolerance<br />No cumulative toxicity<br />Maintain life qualit...
Meta-analysis: PFS Soon JCO 2009<br />
Meta-analysis: OS Soon JCO 2009<br />
Continuation chemotherapy <br />is not standard-of-careBelani ASCO 2010<br />
Continuation of Bevacizumab ?Sandler NEJM 2006;  Reck JCO 2009<br />E4599: cont. 53%<br />AVAiL : cont. 41-42%<br />
Switch to Pemetrexed: JMENCiuleanu ASCO 2008, Lancet Oncol 2010<br />Gem / Platin<br />Pac /  Platin<br />Doc / Platin<br ...
JMEN: HistologyBelani ASCO 2009, Ciuleanu Lancet 2009<br />
JMEN : initial ResponseCiuleanu, Lancet 2009<br />OS for non-squamous:<br />HR<br />CR/PR<br />0.81<br />0.61<br />SD<br /...
JMEN : ToxicityCiuleanu, Lancet 2009<br />Relevant grade 2 toxicities<br />Fatigue<br />Nausea		20 %<br />Anorexie<br />
Switch to Erlotinib: SATURNCappuzzo ASCO 2009 / Lancet Oncol 2010<br />
SATURN: OSCappuzzo, Lancet Oncol 2010<br />
SATURN: SubgroupsCappuzzo, Lancet Oncol 2010<br />
Response to Firstline TherapyCappuzzo, Lancet Oncol 2010<br />
SATURN: EGFR MutationBrugger, ASCO 2009<br />EGFR mutation<br />EGFR wild type<br />HR=0.10 (0.04–0.25)<br />HR=0.78 (0.63...
What did we learn from these <br />registration trials ?<br />Maintainance therapy is an approved option <br />Histology i...
Ongoing Phase III Trials<br />
Large Cell<br />Small Cell<br />Squamous<br />Adeno<br />M. Gugger, Bern University <br />
Predictive Markers for ChemotherapyGandara, Curr Opin Oncol 2010<br />Histology is a predictive factor for<br />pemetrexed...
TS and Drug ResistanceOzasa, Cancer Sci 2010<br />23<br />
SAKK19/09 (BIOPRO)Multicenter phase II trial<br />
EGFR T790M Kobayashi, NEJM 2005<br />25<br />
Case 1: EGFR mutation<br />15 MAR 2010<br />18 MAR 2011<br />Erlotinib<br />28<br />
EGFR-TKI and Line of TherapyMok ESMO 2010, Rosell NEJM 2009<br />
Case 2: ALK Translocation<br />Crizotinib<br />19 FEB 2011<br />17 MAR 2011<br />
ALK-FISHJ. Diebold, Pathology Luzern<br />HE: Adenocarcinoma with signet ring cells<br />ALK FISH (break apart probe): pos...
ALK Inhibitor Crizotinib Kwak, NEJM 2010<br />pretreated = 94%<br />
ETOP<br />LUNGSCAPE<br />
Sequential TestingHorn, JCO 2009<br />
Parallel TestingKim AACR 2010+11<br />
Circulating DNAJCO 2004/Cancer Lett 2007<br />mKRAS<br />wtKRAS<br />
Mok, IPASS 2010<br />
Emerging markers: FGFR Weiss, Science Translat Med 2010<br />
Perspectives Gandara 2010<br />
Enroll patients in clinical trials<br />If not possible, consider switch maintenance if SD, good PS or symptomatic <br />P...
Disclosure Slide<br />Chair of investigator-initiated clinical trials supported by Roche, Eli Lilly, AMGEN, Bayer<br />Adv...
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Gene Profiling in Clinical Oncology - Slide 3 - O. Gautschi - Do we know how to chose the best maintenance treatment?

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Gene Profiling in Clinical Oncology - Slide 3 - O. Gautschi - Do we know how to chose the best maintenance treatment?

  1. 1. Do we know how to choose the <br />best maintenance treatment?<br />oliver.gautschi@onkologie.ch<br />
  2. 2. Firstline therapy (metastatic disease)<br />Continuation maintenance<br />Switch maintenance<br />Secondline therapy (at progression)<br />2<br />Definitions<br />
  3. 3. Delay tumor progression<br />Prolong survival<br />Optimal tolerance<br />No cumulative toxicity<br />Maintain life quality<br />3<br />Aims and Expectations<br />
  4. 4. Meta-analysis: PFS Soon JCO 2009<br />
  5. 5. Meta-analysis: OS Soon JCO 2009<br />
  6. 6. Continuation chemotherapy <br />is not standard-of-careBelani ASCO 2010<br />
  7. 7. Continuation of Bevacizumab ?Sandler NEJM 2006; Reck JCO 2009<br />E4599: cont. 53%<br />AVAiL : cont. 41-42%<br />
  8. 8. Switch to Pemetrexed: JMENCiuleanu ASCO 2008, Lancet Oncol 2010<br />Gem / Platin<br />Pac / Platin<br />Doc / Platin<br />No PD<br />PS 0,1<br />
  9. 9. JMEN: HistologyBelani ASCO 2009, Ciuleanu Lancet 2009<br />
  10. 10. JMEN : initial ResponseCiuleanu, Lancet 2009<br />OS for non-squamous:<br />HR<br />CR/PR<br />0.81<br />0.61<br />SD<br />1.2<br />1.0<br />0.8<br />0.6<br />0.4<br />Favours pemetrexed<br />Favours placebo<br />
  11. 11. JMEN : ToxicityCiuleanu, Lancet 2009<br />Relevant grade 2 toxicities<br />Fatigue<br />Nausea 20 %<br />Anorexie<br />
  12. 12. Switch to Erlotinib: SATURNCappuzzo ASCO 2009 / Lancet Oncol 2010<br />
  13. 13. SATURN: OSCappuzzo, Lancet Oncol 2010<br />
  14. 14. SATURN: SubgroupsCappuzzo, Lancet Oncol 2010<br />
  15. 15. Response to Firstline TherapyCappuzzo, Lancet Oncol 2010<br />
  16. 16. SATURN: EGFR MutationBrugger, ASCO 2009<br />EGFR mutation<br />EGFR wild type<br />HR=0.10 (0.04–0.25)<br />HR=0.78 (0.63–0.96)<br />1.0<br />0.8<br />0.6<br />0.4<br />0.2<br />0<br />1.0<br />0.8<br />0.6<br />0.4<br />0.2<br />0<br />Log-rank p<0.0001 <br />Log-rank p=0.0185<br />PFS probability<br /> 0 8 16 24 32 40 48 56 64 72 80 88 96<br /> 0 8 16 24 32 40 48 56 64 72 80 88 96<br />Time (weeks)<br />Time (weeks)<br />
  17. 17.
  18. 18. What did we learn from these <br />registration trials ?<br />Maintainance therapy is an approved option <br />Histology is predictive for pemetrexed<br />EGFR mutations are predictive for erlotinib<br />but it is still not proven if maintenance offers a true survival advantage over secondline therapy with the same drug given at the right time<br />
  19. 19. Ongoing Phase III Trials<br />
  20. 20. Large Cell<br />Small Cell<br />Squamous<br />Adeno<br />M. Gugger, Bern University <br />
  21. 21. Predictive Markers for ChemotherapyGandara, Curr Opin Oncol 2010<br />Histology is a predictive factor for<br />pemetrexed, gemcitabine and bevacizumab.<br />Are molecular markers better ? Candidates: <br />TTF1, ERCC1, TS, BRCA1, gene signatures<br />
  22. 22.
  23. 23. TS and Drug ResistanceOzasa, Cancer Sci 2010<br />23<br />
  24. 24. SAKK19/09 (BIOPRO)Multicenter phase II trial<br />
  25. 25. EGFR T790M Kobayashi, NEJM 2005<br />25<br />
  26. 26.
  27. 27.
  28. 28. Case 1: EGFR mutation<br />15 MAR 2010<br />18 MAR 2011<br />Erlotinib<br />28<br />
  29. 29. EGFR-TKI and Line of TherapyMok ESMO 2010, Rosell NEJM 2009<br />
  30. 30. Case 2: ALK Translocation<br />Crizotinib<br />19 FEB 2011<br />17 MAR 2011<br />
  31. 31. ALK-FISHJ. Diebold, Pathology Luzern<br />HE: Adenocarcinoma with signet ring cells<br />ALK FISH (break apart probe): positive (patient)<br />IHC: TTF1 +<br />ALK FISH (break apart probe): negative control<br />
  32. 32. ALK Inhibitor Crizotinib Kwak, NEJM 2010<br />pretreated = 94%<br />
  33. 33. ETOP<br />LUNGSCAPE<br />
  34. 34. Sequential TestingHorn, JCO 2009<br />
  35. 35. Parallel TestingKim AACR 2010+11<br />
  36. 36. Circulating DNAJCO 2004/Cancer Lett 2007<br />mKRAS<br />wtKRAS<br />
  37. 37. Mok, IPASS 2010<br />
  38. 38. Emerging markers: FGFR Weiss, Science Translat Med 2010<br />
  39. 39. Perspectives Gandara 2010<br />
  40. 40. Enroll patients in clinical trials<br />If not possible, consider switch maintenance if SD, good PS or symptomatic <br />Pemetrexed if non-SQ and not pretreated <br />Erlotinib if SQ or previous pemetrexed or oral drug preferred<br />Test for EGFR and ALK<br />Recommendations<br />
  41. 41. Disclosure Slide<br />Chair of investigator-initiated clinical trials supported by Roche, Eli Lilly, AMGEN, Bayer<br />Advisory role for AstraZeneca<br />No stocks<br />No employment<br />

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