Introduction: Overview of Current Status of Lung Cancer Predictive Biomarkers

Transcription

1 Introduction: Overview of Current Status of Lung Cancer Predictive Biomarkers

2 Program 7:15 7:40 Translocations as predictive biomarkers in lung cancer: Overview Mari Mino Kenudson, MD 7:40 8:05 Translocation screening with immunohistochemistry Lynette Sholl, MD 8:05 8:25 Translocation testing by next generation sequencing Bryce Portier, MD, PhD 8:25 8:50 Mutations as predictive biomarkers in lung cancer: Overview Kirtee Raparia, MD 8:50 9:15 Role of immunohistochemistry in mutation testing Keith Kerr, MD 9:15 9:40 Predictive biomarker testing in cytology specimens Natasha Rekhtman. MD, PhD 9:40 10:00 Interface of oncology and pathology in targeted therapy of lung cancer Fred Hirsch, MD, PhD

3 Context for Current Status of Lung Cancer Predictive Biomakers Current status of lung cancer Recent developments in lung cancer emerging roles of the pathologist Prior Status of Lung Cancer Predictive Biomarkers Recent developments in targeted therapy and clinical trials

4 Context for Current Status of Lung Cancer Predictive Biomakers Current status of lung cancer Recent developments in lung cancer emerging roles of the pathologist Prior Status of Lung Cancer Predictive Biomarkers Recent developments in targeted therapy and clinical trials

5 The most common causes of cancer death worldwide are cancers of: lung (1,590,000 deaths) liver (745,000 deaths) stomach (723,000 deaths) colorectal (694,000 deaths) breast (521,000 deaths) esophageal cancer (400,000 deaths)

6 Context for Current Status of Lung Cancer Predictive Biomakers Current status of lung cancer Recent developments in lung cancer emerging roles of the pathologist Prior Status of Lung Cancer Predictive Biomarkers Recent developments in targeted therapy and clinical trials

7 Lung Cancer Screening Guidelines and Recommendations Organization Groups eligible for screening Year American Academy of Family Practice 1 Evidence is insufficient to recommend for or against screening American Association for Thoracic Surgery 2 1. Age 55 to 79 years with 30 pack year smoking history. 2. Long-term lung cancer survivors who have completed 4 years of surveillance without recurrence and who can tolerate lung cancer treatment following screening to detect second primary lung cancer until the age of Age 50 to 79 years with a 20 pack year smoking history and additional comorbidity that produces a cumulative risk of developing lung cancer 5% in 5 years CDC American Cancer Society 3 American College of Chest Physicians 4 American College of Chest Physicians and American Society of Clinical Oncology 5 American Lung Association 6 National Comprehensive Cancer Network 7 U.S. Preventive Services Task Force 8 Age 55 to 74 years with 30 pack year smoking history, who either currently smoke or have quit within the past 15 years, and who are in relatively good health. Age 55 to 74 years with 30 pack year smoking history, who either currently smoke or have quit within the past 15 years. Age 55 to 74 years with 30 pack year smoking history, who either currently smoke or have quit within the past 15 years. Age 55 to 74 years with 30 pack year smoking history and no history of lung cancer. 1. Age 55 to74 years with 30 pack year smoking history and smoking cessation < 15 years. 2. Age 50 years and 20 pack year smoking history and 1 additional risk factor (other than secondhand smoke exposure). b Age 55 to 80 years with 30 pack year smoking history and smoking cessation < 15 years

8 February 5, 2015 Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439N) The Centers for Medicare & Medicaid Services (CMS) has determined that the evidence is sufficient to add a lung cancer screening counseling and shared decision making visit, and for appropriate beneficiaries, annual screening for lung cancer with low dose computed tomography (LDCT), as an additional preventive service benefit under the Medicare program only if all of the following criteria are met:

9 WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Fourth edition Travis, W.D., Brambilla, E., Burke, A.P., Marx, A., Nicholson, A. G.

10 2015 Physician Quality Reporting System (PQRS) Lung cancer reporting (biopsy/cytology specimens) Pathology reports based on biopsy and/or cytology specimens with a diagnosis of non small cell lung cancer classified (NSCLC) into specific histologic type or classified as NSCLC NOS with an explanation included in the pathology report Lung cancer reporting (resection specimens) Pathology reports based on resection specimens with a diagnosis of primary lung carcinoma that include the pt category, pn category and, for NSCLC, histologic type

11 Context for Current Status of Lung Cancer Predictive Biomakers Current status of lung cancer Recent developments in lung cancer emerging roles of the pathologist Prior Status of Lung Cancer Predictive Biomarkers Recent developments in targeted therapy and clinical trials

12 Published Online: April 3, 2013 Archives of Pathology & Laboratory Medicine (CAP), Journal of Thoracic Oncology (IASLC) and Journal of Molecular Diagnostics (AMP)

13 ASCO Endorses CAP/IASLC/AMP Guideline on EGFR and ALK Molecular Testing for Patients with Lung Cancer FOR IMMEDIATE RELEASE: October 13, 2014 Contact: Kirsten Goldberg ALEXANDRIA, Va. -- The American Society of Clinical Oncology (ASCO) today issued an endorsement of the joint College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) clinical practice guideline on molecular testing for selection of patients with lung cancer for therapies targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). The guideline defines which patients should be offered EGFR and ALK genetic testing, and when and how such testing should be performed. ASCO's endorsement provides doctors much-needed direction in a rapidly moving field.

14 Published Online: June 28, 2013 Print: February 2014

15 Current Lung Cancer Predictive Biomarkers Two clinically validated and Food and Drug Administration approved lung cancer predictive biomarkers EGFR and ALK occur in only about 20% of lung adenocarcinomas Acquired resistance develops to first generation drugs Search for new biomarkers, new drugs, etc.

16 Context for Current Status of Lung Cancer Predictive Biomakers Current status of lung cancer Recent developments in lung cancer emerging roles of the pathologist Prior Status of Lung Cancer Predictive Biomarkers Recent developments in targeted therapy and clinical trials

17 Second Generation EGFR TKI FDA Approval 2013

18 Second Generation ALK TKI FDA Approval 2014

19 Ceritinib Clinical Trials Phase 1 trial: ASCEND 1 Phase 3: LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib Phase 3: LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non small Cell Lung Cancer

20 Alectinib Alectinib is another second generation ALK TKI Alectinib in phase 3 clinical trials ALEX Study: A Randomized, Phase III Study Comparing Alectinib With Crizotinib in Treatment Naive Anaplastic Lymphoma Kinase (ALK) Positive Advanced Non Small Cell Lung Cancer (NSCLC) Patients

21 The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST ALCHEMIST Screening component (A151216) Coordinated by the Alliance for Clinical Trials in Oncology; Principal Investigators: Pasi A. Janne, M.D., Ph.D., and Geoffrey Oxnard, M.D., Dana Farber Cancer Institute, Boston. ALCHEMIST EGFR Treatment component (A081105) Coordinated by the Alliance for Clinical Trials in Oncology; Principal Investigator: Ramaswamy Govindan, M.D., Washington University, St. Louis. ALCHEMIST ALK Treatment component (E4512) Coordinated by ECOG ACRIN; Principal Investigator: David E. Gerber, M.D., University of Texas Southwestern Medical Center at Dallas.

22 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Lung MAP: S1400 Biomarker Targeted Second Line Therapy in Treating Patients With Recurrent Stage IIIB IV Squamous Cell Lung Cancer Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non Squamous Non Small Cell Lung Cancer Erlotinib Hydrochloride in Treating Patients With Stage IB IIIA Non Small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial) Crizotinib in Treating Patients With Stage IB IIIA Non small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial) Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non Small Cell Lung Cancer That Cannot Be Removed By Surgery Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non Small Cell Lung Cancer That Cannot Be Removed by Surgery

23 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer or Metastatic Large Cell Neuroendocrine Non small Cell Lung Cancer Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non Small Cell Lung Cancer That Cannot Be Removed by Surgery Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non Small Cell Lung Cancer (Cetuximab Closed as of 05/14/10) BATTLE 2 Program: A Biomarker Integrated Targeted Therapy Study

24 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Molecular Profiling and Targeted Therapy for Advanced Non Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies A Randomized Phase II Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma. Modulation of Autophagy in Patients With Advanced/Recurrent Non small Cell Lung Cancer Phase II Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non small Cell Lung Cancer NCI MPACT: Molecular Profiling Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors Erlotinib Hydrochloride Before Surgery in Treating Patients With Stage III Non Small Cell Lung Cancer

25 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Combination Vaccine Immunotherapy (DRibbles) for Patients With Definitively Treated Stage III Non small Cell Lung Cancer Nintedanib in Treating Patients With Advanced Non Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non Small Cell Lung Cancer That Has Progressed After Crizotinib Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non small Cell Lung Cancer Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas Safety Study of MGAH22 in HER2 positive Carcinomas

26 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection Tumor Cell Vaccines With ISCOMATRIX Adjuvant and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers and Malignant Pleural Mesotheliomas Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction Vaccine Therapy With or Without Sirolimus in Treating Patients With NY ESO 1 Expressing Solid Tumors Exemestane, Pemetrexed Disodium, and Carboplatin in Treating Post Menopausal Women With Stage IV Non Small Cell Lung Cancer Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

27 ONGOING TARGETED THERAPY CLINICAL TRIALS IN UNITED STATES Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non Small Cell Lung Cancer INC280 and Erlotinib Hydrochloride in Treating Patients With Non small Cell Lung Cancer Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non small Cell Lung Cancer That Cannot Be Removed by Surgery Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas Ganetespib and Ziv Aflibercept in Refractory Gastrointestinal Carcinomas, Non Squamous Non Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas Low Dose Acetylsalicylic Acid in Treating Patients With Stage I III Non Small Cell Lung Cancer Genetic Sequencing Informed Targeted Therapy in Treating Patients With Stage IIIB IV Non small Cell Lung Cancer

28 And Now The Current Status of Lung Cancer Predictive Biomarkers