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14th Annual International Lung Cancer Congress®

14th Annual International Lung Cancer Congress®


Resources

14th Annual International Lung Cancer Congress®: Meeting-in-a-Box
The Meeting-in-a-Box components are designed for you to share the information with colleagues, fellows, and other health care professionals.

PER Pulse™ Recap
Three PER Pulse™ Recaps presenting key topics from the 14th Annual International Lung Cancer Congress®, which was held on July 25-27, 2013. 




PER Meeting in a Box


Presentation Title Faculty Discussion Question
Optimal Application of Adjuvant Therapy in NSCLC Silvia Novello, MD, PhD Do you recommend adjuvant chemotherapy for patients with stage II or stage III NSCLC? Do you consider it for selected patients with stage IB disease? If so, which patients? Are there sufficient data to support the use of biomarkers such as ERCC1 or RRM1 to guide adjuvant treatment decisions? Do you currently use targeted agents in the adjuvant setting (ie, EGFR or ALK inhibitors, or antiangiogenic agents)?
Endobronchial Ultrasound Ken Y. Yoneda, MD What are the potential advantages of endobronchial ultrasound for staging patients with NSCLC? Can endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) be used to collect sufficient tissue samples for molecular testing? How does endoscopic esophageal ultrasound (EUS) + EBUS compare with mediastinoscopy? Is this the new staging standard?
Mediastinoscopy Stephen G. Swisher, MD, FACS In which patients with negative PET and CT scans would mediastinoscopy  be recommended? What are the strengths and weaknesses of mediastinoscopy compared with EBUS? When should mediastinoscopy be used for staging patients with NSCLC?
Surgical Resection Dominique Grunewald, MD, PhD How is pulmonary function assessed in your practice (or at your institution) when considering suitability for surgery in patients with early-stage NSCLC? Would you consider sublobar resection for a patient with T1 NSCLC and poor pulmonary function? Which sublobar approach yields better outcomes – wedge resection or segmentectomy? How does the incidence of intraoperative complications compare between open thoracotomy lobectomy versus video-assisted thoracoscopic lobectomy?
Role of the Pulmonologists in Diagnosis and Treatment Selection for Lung Cancer Paul Baas, MD, PhD What role do pulmonologists play in the management of patients with NSCLC at your institution?
State of the Art: Multimodality Therapy Everett E. Vokes, MD Is there an optimal chemotherapy regimen to pair with concurrent radiation therapy? Is there a role for targeted biologic agents in combined modality regimens at the present time? Should cetuximab be used? Is there an optimal radiation dose in the treatment of stage IIIB NSCLC?
Surgical Approaches to Locally Advanced NSCLC Hisao Asamura, MD Can a multimodality approach improve the prognosis of patients with superior sulcus tumors? Is such an approach feasible?  Can surgery play a role in the treatment of patients with stage IIIA-N2 disease? What about in patients with T4 tumors invading neighboring structures?
Optimizing the Dose and Schedule of Radiation Therapy in Stage III NSCLC Walter J. Curran, Jr, MD What are the implications of results from the RTOG 0617 study (comparing conventional versus high-dose radiation therapy) for practice?
Integration and Targeted Agents Into Combined Modality Therapy for NSCLC Corey J. Langer, MD, FACP Is there currently a role for targeted agents in chemoradiation regimens for locally advanced NSCLC? Have any agents demonstrated a survival advantage after concurrent chemoradiation for locally advanced NSCLC compared with either placebo or observation? What are some potential reasons for the disappointing results observed with some agents when they have been integrated into chemoradiation regimens?
Keynote: State of the Art: Lung Cancer Paul Bunn, Jr, MD What is known about mechanisms of acquired resistance to EGFR or ALK tyrosine kinase inhibitors (TKIs)? What investigational approaches are showing the most promise for treating NSCLC that has developed resistance to EGFR or ALK TKIs?
Antiangiogenic Agents Heather A. Wakelee, MD How do bevacizumab-associated toxicities compare in elderly patients versus younger patients? Can anticoagulation therapy be administered concurrently with bevacizumab-containing chemotherapy? Is bevacizumab contraindicated in patients with brain metastases? In patients who receive bevacizumab as part of their first-line therapy, do you recommend continuing with maintenance bevacizumab? In the LUME-Lung-1 trial, what impact did adding nintedanib to docetaxel as second-line therapy have on progression-free and overall survival?
ALK Inhibitors Tianhong Li, MD, PhD Based on results from the PROFILE 1007 trial, how does crizotinib compare with docetaxel or pemetrexed in patients with NSCLC with ALK translocations? How did the activity of the second-generation ALK inhibitor LDK378 in crizotinib-pretreated patients compare with the activity in a crizotinib-naïve population?
c-Met Inhibitors Alex A. Adjei, MD, PhD, FACP What is the rationale for investigating MET inhibitors in NSCLC?
Immunotherapy in Lung Cancer David P. Carbone, MD, PhD What is the rationale for investigating immunotherapies for the treatment of lung cancer? How are the agents currently being investigated different from earlier generations of immune-targeted therapies? How do tumors evade immune surveillance? Are responses with investigational immune checkpoint inhibitors durable?
Incorporating Next-Generation Sequencing for Molecular Profiling: Future Implications for Treatment Philip C. Mack, PhD What are the strengths and limitations of next-generation sequencing technologies? Do you expect multiplexed biomarker analysis to become standard for patients with NSCLC in the near future?
Mesothelioma Harvey I. Pass, MD Which somatic and/or germline mutations in mesothelioma have been associated with a familial cancer syndrome? What changes to mesothelioma staging guidelines were made recently, and why?
Current Approaches for LD-SCLC Laurie Gaspar, MD Do you discuss prophylactic cranial irradiation with your patients who have small cell lung cancer? Have any strategies been shown to reduce the risk of neurocognitive deficits following percutaneous coronary intervention (PCI)? Do you discuss memantine with your patients undergoing PCI?
How I Treat: ED-SCLC Primo Lara, Jr, MD Is platinum sensitivity status still considered a relevant prognostic indicator in patients with relapsed extensive-stage SCLC? Which factors were associated with worse survival outcomes in a recent SWOG analysis?
Approaches to Therapy of Metastatic NSCLC: Second-line and Beyond Roy S. Herbst, MD, PhD Approximately what percentage of patients in your practice with advanced NSCLC receive second- or third-line therapy? Do you rebiopsy your patients when their disease progresses? How are clinical trial designs changing in the era of targeted therapies and personalized medicine?
Keynote: Individualized Therapy in Lung Cancer: Where are We in 2013? Giorgio V. Scagliotti, MD, PhD  
Biomarkers for Personalized Lung Cancer Therapy Fred R. Hirsch, MD, PhD What are the crucial biomarkers to test for before initiating treatment for advanced NSCLC? Is EGFR mutation status also important for decision making regarding maintenance therapy or second-line therapy? How does the lab you use screen for ALK gene rearrangement? Is KRAS mutation status important for making treatment decisions in advanced NSCLC?
The Role of Molecular Diagnostics Tetsuya Mitsudomi, MD, PhD Should clinical background be used to determine which patients with advanced NSCLC (adenocarcinoma) should have molecular testing performed? Do you test for EGFR mutation status in former or current smokers?
Master Protocol Designs for Implementing Personalized Medicine Roy S. Herbst, MD, PhD  
Optimizing Care for Special Populations in Lung Cancer (Women, Elderly, PS2) Rogerio C. Lilenbaum, MD What is the optimal management strategy for a patient with advanced NSCLC and a performance status of 2? Would you ever consider using a platinum agent in this patient population?





PER Pulse™ Recap

PER Pulse™ Recap
Medical Writer: Dru S. Dace, PhD



1 of 3
PER Pulse™ Recap
14th Annual International Lung Cancer Congress®
State-of-the-Art Treatment of Advanced Lung Cancer 

The 14th Annual International Lung Cancer Congress®, which was held July 25-27, 2013, was convened to provide current, practical information on the management of lung cancer, as well as look at the novel agents and strategies that will shape the future of lung cancer care. This first of 3 PER Pulse™ Recaps from the International Lung Cancer Congress is centered on the state-of-the-art treatment for advanced lung cancer.
  • Dr. Heather Wakelee discussed the latest data on antiangiogenic agents for the treatment of advanced lung cancer. The angiogenic switch results in the change of tumors from small, dormant, nonvascular ones to those that are larger and exceedingly vascular with high metastatic potential. Bevacizumab has been studied in advanced non-small cell lung cancer (NSCLC) in both the phase III ECOG 4599 and AVAiL studies, demonstrating significantly higher response and progression-free survival (PFS) (as well as overall survival [OS] in the ECOG 4599 study). In addition to monoclonal antibodies, a number of small-molecule antiangiogenic tyrosine kinase inhibitors (TKIs) have been studied in NSCLC, including cediranib, sorafenib, motesanib, and vandetanib. Although PFS and response benefit have been demonstrated with several of these agents, to date, no significant improvement in OS has been demonstrated. Several biomarkers for antiangiogenic therapy have been explored across several tumor types. Investigational biomarkers include hypertension and expression of ICAM, VEGF/VEGFR, VEGF SNPs, IL-6, and IL-12.
     
  • Dr. David Carbone delivered a presentation on lung cancer immunotherapy. Immunotherapy has multiple advantages, in that the immune system has evolved to detect and eliminate “non-self” while not demonstrating toxicity against “self.” Additionally, the immune system has multiple mechanisms to deliver antitumor activity, including the use of natural killer cells, granulocytes, macrophages, T-cells, and antibody-dependent cellular toxicity. Several agents that take advantage of the immune system are being investigated in NSCLC. Ipilimumab, which targets CTLA-4 on T-cells, demonstrated hazard ratios of 0.55 and 0.48 for PFS and OS, respectively, in squamous cell carcinoma (SCC) when combined with chemotherapy. A phase III study of ipilimumab in SCC is currently in progress. PD-1 and PD-L1 are important regulators of the immune system, and several agents that target PD-1 and PD-L1 are under clinical investigation. The most advanced in clinical development is nivolumab, which in a phase I trial in advanced NSCLC demonstrated a 17% objective response rate and 2.3 month PFS. Nivolumab is currently being examined in phase III trials in multiple tumor types.  
Other important state-of-the-art treatment in advanced lung cancer topics that were discussed included:
  • Keynote: State of the Art: Lung Cancer  by Paul Bunn, Jr, MD
  • ALK Inhibitors by Tianhong Li, MD, PhD
  • C-Met Inhibitors by Alex A. Adjei, MD, PhD, FACP
  • Incorporating Next-Generation Sequencing for Molecular Profiling: Future Implications for Treatment by Philip C. Mack, PhD
For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 14th Annual International Lung Cancer Congress®, as well as downloadable slides summarizing results from the meeting.



2 of 3
PER Pulse™ Recap 
14th Annual International Lung Cancer Congress®
The Next Generation of Agents for Lung Cancer 

The 14th Annual International Lung Cancer Congress®, which was held July 25-27, 2013, was convened to provide current, practical information on the management of lung cancer, as well as look at the novel agents and strategies that will shape the future of lung cancer care. This second of 3 PER Pulse™ Recaps from the International Lung Cancer Congress reviews talks from a workshop on the next generation of agents for lung cancer. 
  • Dr. Primo Lara presented a talk on PARP inhibitors in lung cancer. PARPs are a family of enzymes that repair base excisions in both DNA single- and double-strand breaks. PARPs are often upregulated in cancer and are activated in response to DNA damage. It is suggested that PARP inhibitors cause an increase in DNA single-strand breaks, resulting in tumor cell death by synthetic lethality. However, this occurs only in tumor cells where DNA repair by homologous recombination is hampered. In preclinical models, PARP inhibition potentiates temozolomide, platinums, cyclophosphamide, and radiation. Several PARP inhibitors are currently in development for non-small cell lung cancer (NSCLC), including rucaparib, veliparib, and olaparib, which are all in phase II trials. The early stage of PARP inhibitor clinical investigation leaves many unanswered questions, including the degree and duration of PARP inhibition needed for patient benefit, the role of PARP inhibitors in patients without known defects in DNA repair, and predictive biomarkers for PARP inhibitors.
     
  • Dr. Roy Herbst discussed strategies for targeting KRAS in lung cancer. RAS mutations occur quite frequently in numerous tumor types, especially adenocarcinomas of the lung, biliary tract, colon, and pancreas. Patients with KRAS-mutant lung cancer typically have a different clinical course, often resulting in decreased survival compared to those with KRAS wild-type lung cancer. Since mutations in KRAS can result in the activation of the MEK pathway, several MEK inhibitors are being investigated in KRAS-mutant lung cancer. Selumetinib is a MEK inhibitor that recently demonstrated significantly increased progression-free survival (PFS) (and a trend toward increased overall survival [OS]) in progressive KRAS-mutant NSCLC when combined with docetaxel, compared with docetaxel plus placebo. Selumetinib is another MEK inhibitor under investigation in KRAS-mutant lung cancer. Both agents have similar adverse-event profiles that include rash, fatigue, diarrhea, nausea, and vomiting.   
Other important topics discussed at the workshop regarding the next generation of agents for lung cancer included:
  • New Targets for Lung Cancer: Lessons Learned from the TCGA and Synthetic Lethal Screens by David P. Carbone, MD, PhD
  • Targeting the PI3K/AKT Axis: Picking a Winner by Vassiliki Papadimitrakopoulou, MD
  • Approaches to Inhibiting bFGFR – Are They Ready for Primetime? by Paul Bunn, Jr, MD
  • MEK Inhibition: What Progress Have We Made? by David R. Gandara, MD
Reversing Resistance to EGFR TKIs – Approaches in the Frontline and Refractory Setting by Fred R. Hirsch, MD, PhD

For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 14th Annual International Lung Cancer Congress®, as well as downloadable slides summarizing results from the meeting.



3 of 3
PER Pulse™ Recap 
14th Annual International Lung Cancer Congress®
Maintenance Therapy is the Standard of Care for Lung Cancer

The 14th Annual International Lung Cancer Congress®, which was held July 25-27, 2013, was convened to provide current, practical information on the management of lung cancer, as well as look at the novel agents and strategies that will shape the future of lung cancer care. This final of 3 PER Pulse™ Recaps from the International Lung Cancer Congress focuses on a debate on whether maintenance therapy is the standard of care for lung cancer.
  • For the CON stance that maintenance therapy is not the standard of care, Dr. Glenwood Goss presented supporting data for this claim. Several questions still remain about maintenance therapy for lung cancer. For continuation maintenance, where the induction and maintenance agents are the same, the optimal duration of first-line therapy remains unknown. For switch maintenance, a new and potentially non-cross-resistant agent is introduced immediately after induction therapy, and it is unknown whether the early introduction of this new agent is better than delayed introduction. Dr. Goss presented a table of several clinical studies where overall survival (OS) was not improved with maintenance therapy, including the INFORM and ATLAS trials. A review of four meta-analyses of maintenance trials was inconclusive, with one reporting a significant improvement is OS regardless of maintenance type, two demonstrating improvement in OS for switch but not continuous maintenance therapy, and one reporting no OS benefit for maintenance therapy. Other considerations with maintenance therapy are adverse events (AEs) associated with maintenance and impact on patient quality of life (QoL). No trial has demonstrated an improvement in QoL with maintenance therapy versus observation, and three meta-analyses have reported an increased AE rate in patients receiving maintenance. Finally, the costs associated with maintenance are significant, and this impact on the patient must be considered.
  • For the PRO stance that maintenance therapy is the standard of care, Dr. Karen Kelly discussed clinical studies supporting this argument. Several studies have demonstrated a benefit to maintenance therapy. The JMEN study is a clinical trial that evaluated switch therapy, where patients with advanced non-small cell lung cancer (NSCLC) received a non-pemetrexed platinum doublet induction therapy. Nonprogressors were then randomized in a 2:1 fashion to either pemetrexed or placebo maintenance. From this study, pemetrexed maintenance led to a significant increase in both progression-free survival (PFS) and OS, leading to the approval of pemetrexed for maintenance therapy. Additionally, pemetrexed as a continuation maintenance agent was evaluated in the PARMOUNT study. Patients with untreated NSCLC received an induction therapy of pemetrexed and cisplatin, with nonprogressors randomized 2:1 to either pemetrexed or placebo. Again, pemetrexed maintenance demonstrated a significant increase in both PFS and OS. In addition to single-agent maintenance, combination maintenance has been examined in patients with NSCLC. The AVAPERL trial compared two maintenance arms after induction with bevacizumab, pemetrexed, and cisplatin: either bevacizumab alone or the combination of bevacizumab plus pemetrexed. The combination regimen of bevacizumab plus pemetrexed demonstrated a significant increase in PFS compared with bevacizumab alone, but no benefit in OS was observed. Other agents that have demonstrated a maintenance benefit include gemcitabine, which demonstrated increased PFS compared with observation in the IFCT-GFPC 0502 trial. In addition, the SATURN trial demonstrated that erlotinib maintenance is well tolerated and significantly prolongs PFS compared with placebo. Overall, Dr. Kelly summarized her talk by saying that maintenance therapy maintains disease control, improves PFS and OS, and maintains patient QoL. 
For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 14th Annual International Lung Cancer Congress®, as well as downloadable slides summarizing results from the meeting.


Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

This activity is not approved for AMA PRA Category 1 Credit™.

Supported by educational grants from Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Celgene Corporation, Genentech and Astellas, Lilly USA, LLC and Novartis Pharmaceuticals Corporation.








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