Virtual Library
Start Your Search
C. Manegold
Moderator of
-
+
ED11 - Advanced NSCLC: State-of-the-Art Treatment (ID 280)
- Event: WCLC 2016
- Type: Education Session
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:C. Manegold, C. Zhou
- Coordinates: 12/07/2016, 11:00 - 12:30, Hall C8
-
+
ED11.01 - Systemic Therapy for Advanced Oncogene-Driven NSCLC (ID 6485)
11:00 - 11:25 | Author(s): D.R. Gandara, S. Popat, B. Melosky
- Abstract
- Presentation
Abstract:
Oncogene-driven lung cancer remains the embodiment of personalized medicine. Since the first description of EGFR activating mutations found in patients with what was then called bronchiolalveolar carcinoma of the lung (BAC) in 2004, the topic of oncogene-driven lung cancer has grown rapidly and expanded to now encompass a number of additional mutation- and fusion-related entities. Recent updates to molecular testing guidelines, such as those of IASLC, have added several new oncogenes to the initial EGFR and ALK recommendations, including ROS1 and RET fusions, MET amplification or mutation, and HER2 mutations (1,2,3). Although the efficacy of tyrosine kinase inhibitors (TKI) in the treatment of some of these disease subsets is well established, the treatment decision-making process at the time of each relapse is becoming more complex as our knowledge of resistance pathways grows and more treatment options become available, with 2[nd] and 3[rd] generation drugs now in play. Subtping of progressive disease (PD) in oncogene-driven lung cancer into systemic PD versus oligo-PD or CNS-santuary PD can assist in determining the most appropriate therapeutic approach, as shown in Figure 1 below(4).Further, the methods by which we assess tumor at the time of initial or re-biopsy are also rapidly evolving, from single gene or multiplexed gene panels to highly sensitive and specific next generation sequencing (NGS). Lastly, we and others (4,5) have proposed algorithms for possible substitution of plasma cell free DNA by NGS platforms for tissue re-biopsy or for serial monitoring in plasma, as demonstrated in Figure 2.In this presentation we will present a step-wise approach to molecular testing and personalizing treatment for patients with oncogene-driven NSCLC, focusing on EGFR-mutated and ALK-rearranged subsets, since the treatment paradigms are most well established. We will emphasize some of the real world challenges faced by treating physicians. Decision criteria for selecting the best first-line therapy will be reviewed, the importance of re-biopsy upon disease progression to determine the most appropriate next-line therapy highlighted, and third line therapy and beyond discussed. The emerging role of liquid biopsy for assessment of plasma cell free DNA will be discussed, as well as a rationale for substituting liquid biopsy for initial or repeat tumor biopsy in some clinical settings. Algorithms designed to facilitate treatment decision-making will be presented. Two examples in EGFR-mutated lung cancer are shown below.Figure 1: Algorithm for management by Progressive Disease SubtypingEGFR-mutated NSCLCFigure 1Figure 2: Algorithm for Re-Biopsy and/or Plasma cf DNA AnalysisIn EGFR-mutated NSCLCFigure 2 References 1. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar JS, Squire J et al: Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2013, 8(7):823-859. 2. Leighl NB, Rekhtman N, Biermann WA, Huang J, Mino-Kenudson M, Ramalingam SS, West H, Whitlock S, Somerfield MR: Molecular Testing for Selection of Patients With Lung Cancer for Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Society for the Study of Lung Cancer/Association of Molecular Pathologists Guideline. Journal of Clinical Oncology 2014. 3. Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., ... & Grant, S. C. Non–small cell lung cancer, version 2.2013. Journal of the National Comprehensive Cancer Network, 2013, 11(6), 645-653. 4. Gandara DR, Li T, Lara PN, Kelly K, Riess JW, Redman MW, Mack PC: Acquired resistance to targeted therapies against oncogene-driven non-small-cell lung cancer: approach to subtyping progressive disease and clinical implications. Clinical lung cancer 2014, 15(1):1-6. 5. Oxnard, G. R., Thress, K. S., Alden, R. S., Lawrance, R., Paweletz, C. P., Cantarini, M., ... & Jänne, P. A. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non–small-cell lung cancer. Journal of Clinical Oncology, 2014, JCO667162.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ED11.02 - Systemic Therapy for Advanced Non-Oncogene-Driven NSCLC (ID 6486)
11:25 - 11:50 | Author(s): G.V. Scagliotti
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ED11.03 - Management of Oligo-Metastatic NSCLC (ID 6487)
11:50 - 12:10 | Author(s): J. Kuzdzal
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ED11.04 - Palliative Radiotherapy of Advanced NSCLC (ID 6488)
12:10 - 12:30 | Author(s): K. Dieckmann
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
Author of
-
+
MTE16 - Precision Medicine in NSCLC: Lessons Learned and Perspectives (Ticketed Session) (ID 310)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Strauss 2
-
+
MTE16.02 - Precision Medicine in NSCLC: Lessons Learned and Perspectives (ID 6569)
08:00 - 08:30 | Author(s): C. Manegold
- Abstract
- Presentation
Abstract:
Medical therapy in advanced NSCLC in 2016 is characterized by personalization, individualization, and therapy precision. Not only clinical factors are used for treatment differentiation but also the histological type (squamous versus non-squamous) and the molecular profile (mutant versus wild type). In addition, the complexity of the treatment algorithm has gradually increased over time by the incorporation of a number of approved molecules for 1[st], 2[nd] -, subsequent line therapy (Peters, 2012; Masters, 2015; NCCN, 2016). NSCLC – 1[st]-line-therapy - wild-type: For patients with wild-type non-squamous NSCLC it is generally accepted that upfront platinum based doublet chemotherapy (DCT) remains the backbone for individuals with good performance and that this approach should be modified according to feasibility and tolerability, co-morbidity, and age over 70 years. Progress has been made through pemetrexed, which is recommended as the favorite partner of platinum-based components (Scagliotti; 2008/2011). In addition, it has lately been demonstrated that the extension of induction chemotherapy by single agent pemetrexed until progression - in case of non-progression under four cycles of DCT not containing pemetrexed (switch maintenance) (Ciuleanu, 2009) or containing pemetrexed (continuation maintenance) (Paz-Ares, 2012/2013) - prolongs survival. In this case survival may also be prolonged by erlotinib, when used in the switch maintenance setting, but erlotinib’s benefit seem to be restricted to patients, which have experienced disease stabilization to induction chemotherapy (Cappuzzo, 2010; Coudert, 2012). Bevacizumab, when added to platinum-based to DCT, significantly improves response rate, progression free survival, as well as overall survival in eligible patients (Sandler, 2006/2010; Reck, 2009/2010). In wild-type squamous NSCLC platinum based DCT (no pemetrexed, no bevacizumab) remains standard. Nonetheless, necitumumab has recently shown to improve survival when combined with cisplatin/gemcitabine (Thatcher, 2015). Maintenance therapy in squamous tumors with docetaxel or erlotinib (switch) or gemcitabine (continuation) may be justified in some patients even so study evidence is weaker than for non-squamous tumors (Fidas, 2009; Perol, 2012). NSCLC – 1[st]-line-therapy - mutant: For patients with advanced NSCLC expressing specific molecular features – mainly non-squamous tumors – 1[st]- line treatment with targeted agents has been established. In tumors with EGFR mutations gefitinib, erlotinib, and afatinib have shown to prolong progression free survival over standard chemotherapy (Mok, 2009; Rosell, 2012; Sequist, 2013). In tumors bearing ALK-/ROS1-gene-rearrangements crizotinib has also shown to prolong progression free survival when compared to platinum/pemetrexed. (Solomon, 2014). Therefore, erlotinib, gefitinib or afatinib should be prescribed for patients with tumors bearing EGFR-mutations. For patients with tumors bearing ALK-/ROS1 crizotinib should be prescribed. However, for these patients molecular testing is critical and should be used to select patients for EGFR/ALK/ROS1 targeted therapy. Patients with lung adenocarcinoma should not be excluded from testing on the basis of clinical characteristics (ethnicity, gender, smoking status) (Lindeman, 2013). NSCLC - 2[nd] /subsequent-line therapy - wild-type: In patients with disease progression during or after completion of 1[st ] -line chemotherapy, 2[nd] -, subsequent-line therapy is indicated when the patient remains in good clinical condition. Approved older treatment options include docetaxel, pemetrexed and erlotinib. Two anti-angiogenic agents and two immune-checkpoint inhibitors have recently been added. These include nintedanib and ramucirumab (Reck, 2014; Thatcher, 2015), as well as nivolumab and pembrolizumab (Brahmer, 2015; Borghaei, 2015; Herbst, 2016). Nintedanib/docetaxel increases significantly survival in patients with adenocarcinoma who specifically progressed within 9 months after the start of 1[st]-line therapy, who have experienced disease progression as best response to 1[st]-line therapy and decreases tumor burden and decelerates tumor growth. Nintedanib/docetaxel has been approved in the EU for the treatment of patients with adenocarcinoma. Ramucirumab/docetaxel has also been approved in the US and EU for patients with disease progression on or after DCT for wild-type non-squamous and squamous NSCLC. This approval has been based on phase III study evidence indicating survival advantage in non-squamous NSCLC (statistically significant) and squamous NSCLC (numerically longer). Comparing head-to head nivolumab and docetaxel in patients with squamous and non-squamous NSCLC after failure of DCT has demonstrated superior overall survival in patients receiving nivolumab. Nivolumab has received US and EU approval for advanced NSCLC with progression on or after DCT. Nivolumab appears to be most effective in patients with more than 6 months from completion of the latest treatment regimen to randomization in comparison to patients with less than 3 months to randomization. Pembrolizumab has received approval in the US and EU for patients with advanced NSCLC who’s tumors expressed PD-L1 and who have disease progression on or after chemotherapy. Approval has been based on head-to-head comparison of pembrolizumab and docetaxel in patients with previously treated PD-L1 positive squamous and non-squamous NSCLC, which has demonstrated a significant survival benefit for pembrolizumab. NSCLC-2[nd]/subsequent-line therapy - mutant: Resistance to first and second generation EGFR-TKIs is a multifactorial process with a variety of clinically patterns. Its management requires different, case adapted approaches. Several strategies are currently under investigation, but some have already find its way into todays practice although study evidence is still rather weak. In case of oligoprogression the EGFR-TKI therapy may continue but local therapies (radiation, surgery) should be added. In case of diffuse progression EGFR-TKI therapy may continue, but in combination with chemotherapy; EGFR-TKI therapy may be switched to chemotherapy, but at the moment of chemotherapy resistance patients may be re-exposed to EGFR-TKI therapy; admission to clinical trials offering investigational agents may be a valid option for some patient. Osimertinib has just been approved and is recommended for tumors expressing P790M (Jänne, 2015). In tumors bearing ALK-/ROS-gene-rearrangements ceritinib is approved and recommended in case of crizotinib resistance (Shaw, 2014). Conclusion: During the past ten years the complexity of the treatment algorithm of advanced NSCLC has gradually increased by the incorporation of several approved molecules. Novel immunotherapies have recently changed the management of advanced wild-type NSCLC. Treatment by histo-type and geno-type has been established and it can be assumed by the given speed of growth of molecular information that the process of treatment differentiation will fast continue. Identification of new prognostic and predictive factors undoubtedly will accelerate this process.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P3.04 - Poster Session with Presenters Present (ID 474)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.04-008 - CATS: Computed Tomography-Assisted Thoracoscopic Surgery - A Novel Approach in Patients with Deep Intrapulmonary Lesions of Unknown Dignity (ID 5002)
14:30 - 14:30 | Author(s): C. Manegold
- Abstract
Background:
National Lung Screening Trial using low-dose CT may result in a relative reduction in mortality from lung cancer. Screening programs to be implemented will result in more patients being diagnosed with unclear pulmonary lesions and indicate excisional biopsy. Minimal invasive resection of small, deep intrapulmonary lesions can be challenging as the lesions are difficult to localize during VATS surgery. We introduced an intraoperative cone-beam computed tomography (CBCT) system in a hybrid operating theatre to place a marking wire immediately prior to VATS removal of the suspected lesions.
Methods:
Fifteen patients (5 m, 10 f, median age 63yrs) with solitary, deep intrapulmonary nodules of unknown histological status were identified for intraoperative wire marking. While being under general anaesthesia for VATS, patients were placed on the operating table. and a marking wire was placed within the lesion under 3D laser and fluoroscopic guidance using the CBCT system (Artis zeego, Siemens Healthcare GmbH, Germany). Then wedge resection by VATS was performed in the same setting without any repositioning the patient.
Results:
Complete resection with adequate safety margins was confirmed for all lesions. Marking wire placement facilitated resection in 15 out of 16 lesions. Histologically, mean lesion size was 7.5mm. The mean distance of the lesion to the pleural surface was 15.9mm (mean lesion depth/lesion diameter ratio = 2.3). Eleven lesions proved to be malignant, either primary lung cancer or metastases from prior malignancies. Five lesions turned out to be benign. Mean procedural time for marking wire placement was 35min; mean VATS duration was 36min. There is a learning curve fo the whole team involving anesthesiology, radiology, and thoracic surgery.
Conclusion:
CATS is a new, safe, and effective procedure for minimally invasive resection of small, deeply localized intrapulmonary lesions. The benefits of CATS are: (1) 'one-stop shopping' procedure to locate and remove small lung lesions (2) lower risk for the patient (no patient relocation intraoperatively, no marking wire loss), and (3) no necessity to coordinate scheduling between CT and operating theatre.
