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Scientific Advances in Lung Cancer 2015

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1 Scientific Advances in Lung Cancer 2015
Anne S. Tsao, MD, Giorgio V. Scagliotti, MD, PhD, Paul A. Bunn, MD, David P. Carbone, MD, PhD, Graham W. Warren, MD, PhD, Chunxue Bai, MD, PhD, Harry J. de Koning, MD, PhD, A. Uraujh Yousaf-Khan, MD, Annette McWilliams, M.B.B.S., FRACP, Ming Sound Tsao, MD, FRCPC, Prasad S. Adusumilli, MD, FCCP, Ramón Rami-Porta, MD, Hisao Asamura, MD, Paul E. Van Schil, MD, PhD, Gail E. Darling, MD, FRCSC, Suresh S. Ramalingam, MD, Daniel R. Gomez, MD, Kenneth E. Rosenzweig, MD, Stefan Zimmermann, MD, Solange Peters, MD, PhD, Sai-Hong Ignatius Ou, MD, PhD, Thanyanan Reungwetwattana, MD, MSc, Pasi A. Jänne, MD, PhD, Tony S. Mok, MD, Heather A. Wakelee, MD, Robert Pirker, MD, Julien Mazières, MD, PhD, Julie R. Brahmer, MD, Yang Zhou, PhD, MPH, Roy S. Herbst, MD, PhD, Vassiliki A. Papadimitrakopoulou, MD, Mary W. Redman, PhD, Murry W. Wynes, PhD, David R. Gandara, MD, Ronan J. Kelly, MD, MBA, Fred R. Hirsch, MD, PhD, Harvey I. Pass, MD  Journal of Thoracic Oncology  Volume 11, Issue 5, Pages (May 2016) DOI: /j.jtho Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Survival curves according to treatment arm (chemotherapy versus observation) in the acinar/papillary (A, C, and E) and micropapillary/solid (B, D, and F) subgroups for overall (A and B), disease-free (C and D), and specific disease-free survival (E and F). p Values from log-rank test, hazard ratios (HRs), and 95% confidence intervals (CIs) of treatment effect, which were estimated through a univariable Cox model stratified on trial, are reported for each subgroup and end point. Reprinted with permission from Tsao et al.51 Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 Frequency of molecular aberrations in various driver oncogenes in lung adenocarcinomas and current available drugs against these oncogenic proteins. These frequencies are a combination of data from the Lung Cancer Mutation Consortium and frequencies listed in Shea et al.81 Shown in the boxes are the available drugs in addition to their developmental phase. EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma receptor tyrosine kinase; MET, mesenchymal-to-epithelial transition factor; HER2, erb-b2 receptor tyrosine kinase 2; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; BRAF, B-Raf proto-oncogene, serine/threonine kinase; RET, ret proto-oncogene; NTRK1, neurotrophic tyrosine kinase receptor type 1; PIK3A, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; MEK1, mitogen-activate protein kinase kinase 1; KRAS, Kirsten rat sarcoma viral oncogene homolog. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

4 Figure 3 Overall survival by clinical stage according to the seventh edition (A) and the proposed eighth edition (B) of the tumor, node, and metastasis (TNM) classification. Groupings use the entire database available for the eighth edition. Survival is weighted by type of database submission: registry versus other. Reprinted with permission from Goldstraw et al.86 Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

5 Figure 4 Overall survival by pathological stage according to the seventh edition (A) and the proposed eighth edition (B). Groupings use the entire database available for the eighth edition. Survival is weighted by type of database submission: registry versus other. MST, median survival time; NR, not reached. Reprinted with permission from Goldstraw et al.86 Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

6 Figure 5 Schema of the ALCHEMIST study. *Adjuvant radiotherapy is allowed if indicated; patients who decline adjuvant chemotherapy are eligible. **ALK positivity defined by fluorescence in situ hybridization test. NSCLC, nonsmall cell lung cancer; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma receptor tyrosine kinase; BID, twice daily; Q 2 weeks, every 2 weeks. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

7 Figure 6 Illustration showing the role of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in suppressing antitumor immunity. Available therapies against PD-1 and PD-L1 are shown in the boxes along with their phase of development. IFNγ, interferon gamma; MHC, major histocompatibility complex; PD-L2, programmed death ligand 2; Abs, antibodies; NFκB, nuclear factor kappa light-chain enhancer of activated B cells. Modified with permission from Sznol et al.233 Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

8 Figure 7 Schema of the Lung-MAP (S1400) study. Biomarker-driven substudies will progress to phase III if the study meets its end point and a phase III is feasible, at which point the standard of care arm will be determined. TBD, to be determined; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase positive; CCGA, cell cycle gene alteration positive; FGFR, fibroblast growth factor receptor positive. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

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