Management of advanced non small cell lung cancer

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1 Management of advanced non small cell lung cancer Jean-Paul Sculier Intensive Care & Thoracic Oncology Institut Jules Bordet Université Libre de Bruxelles (ULB)

2 Declaration No conflict of interest to disclose

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4 Histology Stage Molecular tests PS Fitness Comorbidities resectable disease unresectable locoregional disease advanced disease Curative surgery with or without (neo)adjuvant chemotherapy Curative radical irradiation combined with chemotherapy Palliative medical therapy

5 Advanced non-small cell lung cancer There are rare situations where curative treatment is possible : Stage III : induction chemotherapy to reduce the tumour and make it subsequently suitable for surgery or radical radiotherapy. Oligometastatic stage IV (such as single brain or adrenal metastasis): curative surgical treatment for both primary and secondary lesions

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10 62 patients with metastatic sites other than brain or adrenals

11 Advanced NSCLC Key factors to consider: Fitness Comorbidities PS Histology Molecular tests Molecular targets: Personalised therapy No molecular targets: Probabilistic therapy

12 Drugs : new paradigm «old» drugs: large labelling The physician has to define the indications «new» drugs: restricted labelling The physician has to apply the restricted indications

13 Consequences for the trials «old» drugs: The physicians had to define the indications by conducting clinical trials Those trials were mainly academic «new» drugs: The trials are conducted by the industry, mainly for registration purposes Those trials are mainly commercial

14 Consequences for the practitioners Conflict of interest have to be taken into account Industry experts : Contracts Opinion leaders Independent experts: EBM approach Critical review of the literature + personal experience Implementation studies

15 Molecular targets: Personalised therapy Erlotinib Gefitinib Crizotinib

16 Lung adenocarcinoma

17 EGFr

18 Gefitinib IPASS trial (2009)

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20 overall mutation No mutation?

21 Mutation No mutation High copy number Low copy number

22 Exon 19 L858R

23 Gefitinib (EGFr mutation) (2010)

24 Erlotinib (EGFr mutation) (2011)

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28 EML4-ALK

29 crizotinib OR : 57 % (47/82)

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32 Squamous cell lung carcinoma

33 In summary

34 No molecular targets: Probabilistic therapy Generic forms available Cisplatin Ifosfamide Mitomycin C Vindesine Vinblastine Gemcitabine Paclitaxel Docetaxel Vinorelbine Carboplatine? Etoposide? Protected by patents (restricted indications) Pemetrexed Erlotinib Gefitinib Bevacuzimab Crizotinib

35 Which regimen?

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43 Non-squamous cell carcinoma

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47 Which cisplatin dosage?

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53 How many cycles? Maintenance?

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55 Optimal duration of first-line chemotherapy

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62 2 nd line (and further) treatment Generic forms available Cisplatin Ifosfamide Mitomycin C Vindesine Vinblastine Gemcitabine Paclitaxel Docetaxel Vinorelbine Carboplatine? Etoposide Protected by patents (restricted indications) Pemetrexed Erlotinib Gefitinib Bevacuzimab Crizotinib

63 Attitude Repeat initial regime if long free interval after good responses Cisplatin-based chemotherapy after TKI in tumours with activating EGFr mutation Consider drugs which have been shown improving survival Docetaxel Pemetrexed (non squamous cell carcinoma) Erlotinib Search for activating mutations or fusion if not so far done

64 Comorbidities Renal failure Cardiac disease Liver disease Poor PS Elderly

65 Conclusions : 2012 Key factors to consider: Fitness Comorbidities PS Histology Molecular tests Molecular target: Personalised therapy No molecular target: Probabilistic therapy EGFr mut : gefitinib, erlotinib Alk: crizotinib Cisplatin + - Any histology: VNR, gemci, doce, etc. - Non-squamous histology: pemetrexed