Case Studies. Ravi Salgia, MD, PhD

Transcription

1 Case Studies Ravi Salgia, MD, PhD Professor and Arthur & Rosalie Kaplan Chair Medical Oncology and Therapeutics Research Associate Director for Clinical Sciences Research City of Hope

2 Objectives To Understand Current Decision Making for Therapy in Lung Cancer To Understand a Case of ALK Rearrangement To Understand a Case of EGFR Mutation To Understand a Case of Immunotherapy

3 36 y.o. Asian Female, Never-Smoker First presented with walking pneumonia which had been resolved. Later presented to PCP with 2 month history of cough and lump in her throat. Biopsy indicated the lump was benign. CT soft tissue neck revealed a large solid mass in the left lobe of the thyroid. Chest CT indicated left perihilar mass with evidence of metastatic disease to the left hilum, mediastinum, and liver.

4 What to Do Next? A. Perform a biopsy, and potential perform molecular analysis if lung cancer (adenocarcinoma) B. Start Chemotherapy right away C.Refer to Hospice

5 What are Biomarkers? Smoking Radon Familial CT Screening Liquid Biopsies Biopsy and IHC Adapted from: Various Protein Biomarkers EGFR T790M ALK ROS1 MET BRAF Amplification MET RET Histological HER2 Changes NTRK KRAS MSI TMB PD-L1 FGFR, PI3K etc.

6 Macro-Heterogeneity in lung cancer Ngoc et al. Oncology & Hematology, 2017 Lartigue OncLive 2016

7 Micro-Heterogeneity in lung cancer Hensing, Mambetsariev, Salgia; 2017; in Pass et al. IASLC Thoracic Oncology 2 nd Ed.

8 36 y.o. Asian Female, Never-Smoker Initially, obtained bronchoscopy with biopsy, consistent with adenocarcinoma (TTF1+, lung origin) Molecular analysis sent Started Chemotherapy with Carboplatin/Paclitaxel, not well tolerated Molecular analysis returned by NGS- ALKrearrangement identified Would you now: A. Switch chemotherapy B. Start Crizotinib C. Start Erlotinib

9 CNS Progression on Crizotinib

10 What to Do Next A. Switch to chemotherapy with carboplatin/pemetrexed B. Switch to immunotherapy C.Switch to alectinib D.Refer to hospice

11 Key Clinical ALK Targeted Studies in NSCLC Ngoc et al. Oncology & Hematology, 2017

12 51 y.o. Asian Female, Never Smoker Presented to the ER with chest pain and shortness of breath. CT angio revealed a lobulated RUL mass along with right paratracheal adenopathy, subcarinal adenopathy, and leftsided anterior mediastinal adenopathy. MRI showed metastatic disease to the vertebral bodies and brain. Biopsy of the RUL mass consistent with poorly differentiated adenocarcinoma (TTF1 +, Napsin-A +, p40 -). The patient had L858R EGFR mutation. Now, you would start Erlotinib Afatinib Gefitinib

13 Resistance Before Tarceva 3 months on Tarceva Progression on Tarceva (6 mos.)

14 A. Repeat a biopsy What to Do Next B. Perform a liquid biopsy C.Start chemotherapy D.Refer to hospice

15 Primary and acquired resistance to EGFR-TKIs Tong et al. Cancer Letters, 2017

16 Proposed use of liquid biopsy in EGFR-mutated lung cancer Singh et al. Ann Transl Med. 2017

17 Clinical Course -Difficult to do a repeat biopsy (patient could not tolerate) -Obtained Liquid Biopsy -Identified T790M EGFR mutation in the liquid biopsy -Started Osimertinib

18 Key Clinical EGFR targeted studies in NSCLC Ngoc et al. Oncology & Hematology, 2017

19 51 y.o. Caucasian Female with Metastatic NSCLC First presented to the ER with dizziness and high blood pressure. Chest XR revealed left lower lobe mass. CT confirmed LLL mass and indicated mediastinal adenopathy. MRI of the brain showed multiple lesions consistent with metastasis. Biopsy of left lung mass consistent with adenocarcinoma, lung origin. S/p radiation therapy to the brain. Molecular testing results: KRAS G12C mutation. PD- L1 90%.

20 Decision for High PD-L1 What would you advise after brain radiation? A. Start chemotherapy with carboplatin/pemetrexed B. Start chemotherapy with carboplatin/abraxane C. Start immunotherapy with pembrolizumab D. Refer to hospice

21 Mechanism of action of immune checkpoint inhibitors Ngoc et al. Oncology & Hematology, 2017

22 Key Clinical Immune-Oncological Studies Ngoc et al. Oncology & Hematology, 2017

23 Response to Pembrolizumab Before therapy s/p 12 cycles Pembrolizumab

24 Take Home Messages Molecular testing should be part of the SOP for patients with metastatic NSCLC, non-squamous histology Molecular testing can be NGS, and potentially liquid biopsy Actionable genetic alterations such as EGFR, ALK, ROS1, BRAF should utilize targeted therapies After progression on targeted therapy, repeat biopsy should be performed