Dr. Andres Wiernik Lung Cancer
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
~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)
SCC SCLC Adenocarcinoma (exception BA)
Non-Small Cell Lung Cancer (NSCLC)
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%
Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1
65 yo male, former smoker, work-up for knee surgery.cxr
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
Surgical Management in Stage I-II 1) Lobectomy is the preferred option* 1) Thoracotomy 2) VATS 2) Limited (sublobar) resection (wedge, segmentectomy)
Ann Thorac Surg. 1995 Sep;60(3):615-22; discussion 622-3.Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ginsberg RJ, Rubinstein LV.
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
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
Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1
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
N0-1: 5 y OS: 26.6% DON T OPERATE in someone N2: 5y OS : 10.9% with locally advanced disease or distant metastasis
Stage III NSCLC (Locally advanced) Treatment: Some patients might still be Surgical Candidates (IIIA - N1) For Patients with Stage IIIB N2 = Chemotherapy + Radiation
Mediastinal Hilar Subcarinal N2 Bronchopulmonary N1
STAGE IV or Metastatic NSLCL
Treatment Options for Stage IV NSCLC 1. Chemotherapy 2. Target Therapy / Molecular Therapy Adenocarcinoma 3. Immunotherapy
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
Erlotinib response BEFORE AFTER
PFS at 12 months: Gefitinib: 25% Carbo + Paclitaxel 6% NEJM, 2009
Erlotinib BEFORE AFTER
Crizotinib ALK mutation NSCLC BEFORE AFTER
NEJM 2013
Crizotinib BEFORE AFTER
Immune-checkpoint modulators in LUNG CANCER Cancer Immunotherapy for Stage IV Disease PEMBROLIZUMAB NIVOLUMAB
Two landmark papers Phase I studies 1. Topalian SL, et al. Safety, activity, and immune correlates of anti PD-1 antibody in cancer. NEJM 2012 2. Brahmer JR, et al. Safety and activity of anti PD-L1 antibody in patients with advanced cancer. NEJM 2012
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
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
PDL1 IHC in 42 patients: 36% responses among PDL1 positive tumors
PDL1 POSITIVE = PD-L1 expression on at least 50% of tumor cells
PFS Survival
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