Dr. Andres Wiernik. Lung Cancer

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1 Dr. Andres Wiernik Lung Cancer

2 Lung Cancer Facts - Demographics World Incidence: 1 8 million / year World Mortality: 1 6 million / year 5-year survival rates vary from 4 17% depending on stage and regional differences

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7 ~10-15% Lung Cancer ~80-85% Small Cell Lung Cancer (SCLC) Non-Small Cell Lung Cancer (NSCLC) ~60% Adenocarcinoma ~ <5% Large Cell Carcinoma ~30-40% Squamous Cell Carcinoma (SCC)

8 SCC SCLC Adenocarcinoma (exception BA)

9 Non-Small Cell Lung Cancer (NSCLC)

10 NSCLC STAGE Definition Treatment 5-year Survival % at Diagnosis I Tumor less than 5 cms Surgery (+/- Adjuvant chemo) 60-70% OS 16% Localized II Locally Advanced NO mediastinal involvement Surgery + Adjuvant Chemotherapy 40-50% OS III Locally Advanced With mediastinal involvement Surgery + Adjuvant Chemo + XRT OR Chemoradiation alone 5-20% OS 22% Locally Advanced IV Metastatic Palliative Chemotherapy Poor 57%

11 Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1

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13 65 yo male, former smoker, work-up for knee surgery.cxr

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15 Management of early stage (I-II) NSCLC Tobacco Cessation Is he a Surgical Candidate? PFTs DON T OPERATE in someone with Am I sure he does not have mediastinal involvement or distant metastasis? locally advanced disease or distant metastasis PET CT Scan Bronchoscopy Pathological Mediastinal Staging +/- Brain MRI

16 Surgical Management in Stage I-II 1) Lobectomy is the preferred option* 1) Thoracotomy 2) VATS 2) Limited (sublobar) resection (wedge, segmentectomy)

17 Ann Thorac Surg Sep;60(3):615-22; discussion Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ginsberg RJ, Rubinstein LV.

18 NSCLC - Tips ALWAYS PFTs and PET CT scan if surgical candidate Early stage not operable: XRT Locally Advanced not operable: Chemo+XRT Stage III NSCLC is treated with curative intent only when surgery is performed. Pericardial or Pleural involvement = STAGE IV

19 When to give XRT? Inoperable patients XRT alone in stage I Chemoradiation in locally advanced (stage II-III) ANY time for palliation purposes (brain mets, painful bone mets) Positive margins after Sx (if re-resection is not possible) Patients with pathological stage N2 (ANITA trial) or inadequate sampling of N2 LNs bad surgeon! NOT recommended in the adjuvant setting for patients with pathologic stage N0-1 disease as it has been associated with increased mortality

20 Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1

21 Stage III NSCLC (Locally advanced) Goal of treatment is cure Despite this most of the patients with Stage III NSCLC will die from their disease

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23 N0-1: 5 y OS: 26.6% DON T OPERATE in someone N2: 5y OS : 10.9% with locally advanced disease or distant metastasis

24 Stage III NSCLC (Locally advanced) Treatment: Some patients might still be Surgical Candidates (IIIA - N1) For Patients with Stage IIIB N2 = Chemotherapy + Radiation

25 Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1

26 STAGE IV or Metastatic NSLCL

27 Treatment Options for Stage IV NSCLC 1. Chemotherapy 2. Target Therapy / Molecular Therapy Adenocarcinoma 3. Immunotherapy

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29 Mutation / Rearrangement EGFR Frequency Demographics FDA TARGET Potential target (Clinical Trial) 40% Asians 10-20% Non Asians Non-Smokers Women Asians ALK 2-7% Non-Smokers Younger Patients Asians ROS1 1-2% Non-Smokers Women Asians Younger patients Erlotinib Gefitinib Crizotinib several several Crizotinib MET (Exon 14) 4% Crizotinib KRAS 25% Smokers Younger Age Non-asians BRAF 3-5% Females Smokers and Non- Smokers HER-2 <2% Women Non-Smokers Selumetinib Trametinib Abemaciclib Dabrafenib Vemurafenib Trametinib Dacomitinib Trastuzumab T-DM1

30 Erlotinib response BEFORE AFTER

31 PFS at 12 months: Gefitinib: 25% Carbo + Paclitaxel 6% NEJM, 2009

32 Erlotinib BEFORE AFTER

33 Crizotinib ALK mutation NSCLC BEFORE AFTER

34 NEJM 2013

35 Crizotinib BEFORE AFTER

36 Immune-checkpoint modulators in LUNG CANCER Cancer Immunotherapy for Stage IV Disease PEMBROLIZUMAB NIVOLUMAB

37 Two landmark papers Phase I studies 1. Topalian SL, et al. Safety, activity, and immune correlates of anti PD-1 antibody in cancer. NEJM Brahmer JR, et al. Safety and activity of anti PD-L1 antibody in patients with advanced cancer. NEJM 2012

38 296 patients with advanced cancer (1-5 systemic treatments prior) Melanoma NSCLC 47% had at least 3 prior regimens CRCP (prostate) RCC (renal) CRC (colon-rectum) NIVOLUMAB Tx: Anti PD-1 antibody at a dose of 0.1 to 10.0 mg/kg every 2 weeks Response assessment after 8 weeks. Patients received up to 12 cycles (until disease progression or a CR) No MTD (max tolerated dose) was defined

39 Objective Response (CR or PR) Primary Tumor Number of Patients Cumulative Response Rates (different doses) NSCLC 14 / 76 18% (16% - 32%) Melanoma 26 / 94 28% (9% - 41%) RCC 9 / 33 27% (24% - 31%) CRPC? 0% CRC? 0% Responses were durable: 20 of 31 responses lasted 1 year or more NSCLC: SCC and non-scc responded NEJM, 2012

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42 PDL1 IHC in 42 patients: 36% responses among PDL1 positive tumors

43 PDL1 POSITIVE = PD-L1 expression on at least 50% of tumor cells

44 PFS Survival

45 Thank you!