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M. Boyer
Moderator of
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SC31 - Together Against Lung Cancer - A Strategy for Success in the 21st Century (ID 355)
- Event: WCLC 2016
- Type: Science Session
- Track: Regional Aspects/Health Policy/Public Health
- Presentations: 4
- Moderators:M. Boyer, P.E. Postmus
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall C7
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SC31.01 - The Role of Scientific Organizations (ID 6731)
14:30 - 15:45 | Author(s): P.A. Bunn, Jr.
- Abstract
- Presentation
Abstract:
WCLC Extended Abstract: The Role of Scientific Organizations Paul A. Bunn, Jr, MD, FASCO The goal of scientific organizations is to facilitate progress in a specific area through promotion of research, training and education. In some instances the scientific area may be a single discipline such as medical, surgical or radiation oncology, pathology, radiology and so on. In some instances the scientific area may be a single geographic region such as Europe, North America or Asia. Examples of such organizations would be the European Respiratory Society (ERS), the American College of Radiology, the College of American Pathology (CAP) and many, many others. In some instances the organization might focus its efforts on training and research grants and in other instances the organization might focus on education of the public and in public programs such as prevention. In some instances the organization may conduct research or may solely sponsor research to be done by others. Some scientific organization chose to develop guidelines for clinical care. All of these efforts are important and different organizations focus on different aspects of a problem. In this presentation I will focus my attention on The International Association for the Study of Lung Cancer (IASLC) since it is the sponsor of the World Conferences on Lung Cancer and since is programs are dedicated to reducing the world wide burden of thoracic cancers. Lung Cancer is the leading cause of cancer death worldwide and the most preventable. When the IASLC was organized in 1974 it was recognized not only that lung cancer was the leading cancer killer but also that it would take an international and multidisciplinary effort to make progress. The very international and multidisciplinary nature of the IASLC are what set it apart from other organizations. Many of the unique contributions of the IALSC rely on these differentiating aspects. For example, the IASLC has contributed all the cases and evaluation of the world wide lung cancer, mesothelioma and thymoma TNM staging classifications. The IASLC Pathology committee has formulated all of the changes to the pathologic classification of thoracic cancers. The IASLC has worked with other organizations such as the College of American pathology and Association of Molecular Pathology to develop guidelines on molecular characterization of lung cancer. To enhance worldwide collaboration and education the IASLC began the World Conferences on Lung Cancer and rotated these conferences to different regions around the world. Originally, these conferences were held every 3 years as progress was slow but as research and research advances have quickened, the WCLCs are ow held annually. In addition the IASLC sponsors regional meetings on a routine basis including the European Lung Cancer Conference (ELCC), the Latin America Lung Cancer Conference (LALCA), the Asia Pacific Lung cancer conference and the Chicago Multidisciplinary Lung Cancer conference. The IASLC also sponsors workshops on various timely topics such as a conference on Small cell lung cancer held in 2015. To support its educational and research missions the IASLC publishes a scientific journal entitled Journal of Thoracic Oncology which has continually increased its circulation and impact factor. More recently, the IALSC has reinstituted a weekly newsletter and has published monographs on time issues such as ALK and PD-L1 testing. The IASLC has sponsored research grants especially for junior faculty and fellows to support and nurture their research careers. The IASLC has also sponsored travel fellowship awards for junior investigators and for young faculty from developing countries. The IASLC had worked with advocacy groups from around the world to provide information and support to these groups and to individuals and families afflicted by lung cancer. These efforts have led to a sharing of efforts and to publications directed to patients and their families. The IASLC’s tobacco committee has worked tirelessly to combat the worldwide tobacco epidemic. References: Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FRThe International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016.. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23. Review Bunn PA Jr, Minna JD, Augustyn A, et al. Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?J Thorac Oncol. 2016 Apr;11(4):453-74. doi: 10.1016/j.jtho.2016.01.012. Epub 2016 Jan 30. Review Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.J Thorac Oncol. 2016 Jan;11(1):39-51. doi: 10.1016/j.jtho.2015.09.009 Hirsch FR.International Association for the Study of Lung Cancer (IASLC): celebrating 40 years with scientific and educational achievements!J Thorac Oncol. 2014 Oct;9(10):1424-5. doi: 10.1097/JTO.0000000000000340. Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E, Van Schil P; Staging and Prognostic Factors Committee; Advisory Boards. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S88-96. doi: 10.1097/JTO.0000000000000293. Tsao MS, Travis WD, Brambilla E, Nicholson AG, Noguchi M, Hirsch FR; IASLC Pathology Committee. Forty years of the international association for study of lung cancer pathology committee..J Thorac Oncol. 2014 Dec;9(12):1740-9. doi: 10.1097/JTO.0000000000000356. Leighl NB, Rekhtman N, Biermann WA, Huang J, Mino-Kenudson M, Ra malingam 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 Association for the study oflung cancer/association for molecular pathology guideline. J Clin Oncol. 2014 Nov 10;32(32):3673-9. doi: 10.1200/JCO.2014.57.3055. Epub 2014 Oct 13 Hung JJ, Yeh YC, Jeng WJ, Wu KJ, Huang BS, Wu YC, Chou TY, Hsu WH. Predictive value of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in tumor recurrence and patient survival. J Clin Oncol. 2014 Aug 1;32(22):2357-64. doi: 10.1200/JCO.2013.50.1049. Epub 2014 May 5 Detterbeck FC, Asamura H, Crowley J, Falkson C, Giaccone G, Giroux D, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson A, Okumura M, Ruffini E, van Schil P, Stratton K; Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain The IASLC/ITMIG thymic malignancies staging project: development of a stage classification for thymic malignancies. J Thorac Oncol. 2013 Dec;8(12):1467-73. doi: 10.1097/JTO.000000000000001
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SC31.02 - The Role of Patient Advocacy Groups (ID 6732)
14:30 - 15:45 | Author(s): B.J. Addario
- Abstract
- Presentation
Abstract:
The role of Patient Advocacy organizations in the oncology health care delivery ecosystem is ever evolving and has moved well beyond its original role of solely advocating for services, research, care and understanding. The current field of patient advocacy has its roots in the patient rights movement of the 1970’s with groups like The National Welfare Rights Organization being instrumental in getting a patient bill of rights accepted by the Joint Commission on Accreditation of Healthcare Organizations in 1972[1]. The transformation was further accelerated in 1991 with the formation of the FDA Patient Representative Program and has continued to expand over time with patient advocates now being involved in the entire care continuum. In this presentation I will focus my attention on examples of the ever evolving and expanding role of patient advocacy highlighted by projects developed and led by "partner" foundations the Bonnie J. Addario Lung Cancer Foundation (ALCF) and the Addario Lung Cancer Medical Institute (ALCMI). Addressing Disparities in Care The disparities in lung cancer treatment and outcomes among underserved populations are well documented[2]. Further, 80% of cancer patients are treated in the community hospital setting yet may not receive the same level of care as those treated at leading academic centers. The ALCF Community Hospital Centers of Excellence (COE) program addresses this unmet need. The COE program is a patient-centric model for lung cancer that establishes a standard of care for community hospitals which often treat underserved patient populations. The COE program, which currently includes 13 hospitals in regions of high unmet need, aims to improve the standard of care, patient experience and patient outcome by offering patients and caregivers the same type of multi-disciplinary and comprehensive care provided at leading academic centers. ALCF also provides lung cancer education and services to patients, caregivers and the community. The COE program tracks patient process data longitudinally for multiple quality-of-care metrics, including disease stage at diagnosis; molecular testing; tumor board review; time from diagnosis to treatment; treatment type; and clinical trial participation. Site data will also be monitored to provide a contextual picture of the program including total patients seen, demographics, insurance mix, rates and outcomes of molecular testing among other metrics. Data is analyzed across the COE community and against comparator groups to demonstrate impact of the COE program[3]. Accelerating Clinical Trial Accrual The U.S. National Institutes of Health database currently lists over 45,000 cancer-related clinical trials worldwide[4]. Unfortunately, more than 20% of these trials will never complete, for reasons unrelated to the effectiveness of the intervention that’s being tested. The most common reason for 20% of all clinical trials never finishing is poor patient accrual. One of the most common reasons for low accrual is procedural inefficiencies such as complexities in enrolling in the trial itself and the informed consent process. In 2014, ALCMI launched a prospective study to characterize somatic and germline genomics of adolescents and young adult (AYA) patients[5]. It is estimated that less than 2% of those newly diagnosed with lung cancer globally are AYA, thus presenting a striking recruitment challenge. To address this challenge, ALCMI's study workflow included building a dedicated website[3] enabling remote screening and e-consenting so patients could participate from their homes anywhere in the world while, in parallel, ALCF employed social media to educate patients on the importance of comprehensive genomic profiling and increasing awareness of the study via grass-roots patient blogging. Together, ALCMI and ALCF bring "research to the patient". Accrual opened July 23, 2014 and in the first 5 weeks of the study, 37 subjects consented. Of the 37 initially consented, 35 enrolled via the remote web-portal. As of June 15 2016, 104 subjects are enrolled (128 consented) in the study from 10 countries following a social media campaign. Of the 104 subjects enrolled to date, 49% entered the study via the remote study portal with the balance recruited locally by participating ALCMI study sites Conclusion As briefly outlined above, patient advocacy organizations have moved well beyond their original patient supportive role and have become key players in the oncology healthcare delivery and clinical research ecosystems. As the healthcare system continues to evolve and become more complex so will the role of patient advocacy organizations. To address these challenges, there will be even greater need for innovation, sharing of data and resources, increased infrastructure and mission sophistication, the need to avoid overlap and duplication, and a laser focus on providing meaningful improvement in the availability, transparency and affordability of healthcare. References: 1. Ruth R. Faden, Tom L. Beauchamp, A History and Theory of Informed Consent, (Oxford University Press, 1986), 93 2. http://www.gotoper.com/publications/ajho/2015/2015feb/lung-cancer-disparities-in-the-era-of-personalized-medicine 3. Leah Fine[1], Guneet Walia[1], Raymond U. Osarogiagbon[2]; [1]Addario Lung Cancer Foundation, San Carlos/United States of America, [2]Baptist Cancer Center, Memphis, TN/United States of America. The ALCF Centers of Excellence Model Delivers a Standard of Care to the Community Similar to Academic and Research Centers. World Conference on Lung Cancer, Abstract 6334, December 2016 4. https://clinicaltrials.gov. 5. Barbara J. Gitlitz, Alicia Sable-Hunt, Steven W. Young, Andreas Kogelnik, Danielle Hicks, Deborah Morosini, Tiziana Vavala, Marisa Bittoni, S. Lani Park, Silvia Novello, Geoffrey R. Oxnard, Bonnie Addario (in press). Employing Remote Web Consenting and Social Media to Facilitate Enrollment to an International Trial on Young Lung Cancer. World Conference on Lung Cancer, Abstract 4180, December 2016 6. https://www.openmednet.org/site/alcmi-goyl
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SC31.03 - The Role of Medical Journals (ID 6733)
14:30 - 15:45 | Author(s): D. Collingridge
- Abstract
- Presentation
Abstract:
The role of medical journals David Collingridge Editor-in-Chief, The Lancet Oncology and Publishing Director, The Lancet Specialty Journals, 125 London Wall, London EC2Y 5AS, United Kingdom; Clinical Associate Professor of Radiation Medicine, Hofstra/Northwell Health, Lake Success, NY, USA. For many years the traditional peer-reviewed medical journal was seen to be the only reliable place to obtain the latest advances in science and medicine. But, with the advent of online depositiories, information services and feeds, news services, preprint servers, data-sharing, and open access, to name just a few recent innovations, the role of the medical journal is changing. Whilst it is true to say that for many physicians, certain journals are still seen as an authorative voice and a vital source of validated data to inform practice, this isn’t the case for all—indeed, any reasonably reputable source of information, especially if easily available online, is increasingly considered to be a valid fount of medical evidence. So what is the role of the medical journal in the online era? How do medical journals remain relevent, continue to offer a valuable resource of practice-defining information, and play a important and collaborative role with their respective communities? How do medical journals not succumb to the fate of the newspaper or music industries, in which the online revolution has caused considerable upheaval—which many might argue has not resulted in a postive evolutionary change for the betterment of all stakeholders? The central tenet for any medical journal is publication of trustworthy data that have been thoroughly reviewed and challenged prior to publication to ensure the interpretation is accuate, honest, and will not cause harm if used in the real world. Moreover, a good medical journal should be much more than this, and must show leadership; take risks; distil the most important information to a time-poor readership; provide innovative ways of linking disparate, but inter-related, strands of information to a readership that no longer reads cover-to-cover; and encourage scientific debate rather than simply reporting it. A good contemporary medical journal therefore needs to be more than just a mirror reflecting the lastest research or thinking without contest: it must inform and drive research and clinical practice forwards. There are multiple ways in which this can be achieved. First, a journal must offer a impartial platform for presentation of data and discussion of ideas without prejudice, and ensure studies are reported rigourously, transparently, and honestly. The activities of an unconflicted editorial team and well-qualified peer reviewers are vital in this regard, as is the application of reporting standards to ensure all data and analyses are captured accurately. Second, journals have a responsibility to ensure the ethical integrity of everything they publish. Journals should be active members of independent ethics organisations and uphold the highest standards. If any suspicion of misconduct occurs surrounding a published article, reputable journals should always investgiate such allegations, which often relate to issues such as: research conduct; reproducibility of data; unethical behaviour in the laboratory or institution; plagarism; withholding of pertinent data and misreporting; conflicts of interests; authorship disputes; or compliance with prevailing governance structures. Academic institutions take these issues very seriously because of the ramifications for their own integity, and thus journals and instititions must work together to root-out any misconduct and ensure the medical literature is trustworthy and organisations practice science and medicine of the highest standards. Third, journals can help further the practice of good science by taking a leadership role in forward-focused programmes. Recent examples include the team science programmes in the UK and USA, and the REWARD initiative. The UK Academy of Medical Sciences Team Science project has been focused on how biomedical researchers can be encouraged, supported, and rewarded for participating in team-based collaborations—editors and publishers are clear stakeholders in this debate; whilst the REWARD (REduce research Waste And Reward Diligence) campaign encourages everyone involved in biomedical research to critically examine the way they work to reduce waste and maximise efficiency via five guiding principles: setting the right research priorities; using robust research design, conduct, and analysis; making sure regulation and management are proportionate to risks; ensuring all information on research methods and findings are accessible; and guaranteeing reports of research are complete and usable. Finally, a fifth role for medical journals is to take an dynamic part in advocating change, leading the direction of future research, and actively participating in health policy reform and in initiatives to promote universal access to medicine. The Lancet Oncology’s advocacy programme, for example, maps out the inequalities and inequities in health systems worldwide, and highlights deficiencies in all aspects of cancer care, health policy, structural organisation, and leadership. The programme offers a impartial platform that brings together thought-leaders from across different disciplines and organisations to offer solutions to those barriers that hinder provision of high quality cancer control, irrespective of socioeconomic status or country of residence. The journal achieves this via specific, dedicated undertakings including Commissions, series of inter-related papers on specific themes, targeted articles, conferences, and events. The medical journal in the 21[st] century must evolve from being a simple record of research to an engaged stakeholder advocating and leading change in the practice of medicine. Journals should aim to be platforms that bring together communities and thought-leaders rather than disenfranchise groups in to silos. The world has never been as interconnected as it is today, and it is only by working together with a clear vision that journals, hand-in-hand with the communities they serve, will achieve the progress needed to promote the best research and health policies to improve healthcare for all.
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SC31.04 - The Possibilities of Print & Social Media (ID 6734)
14:30 - 15:45 | Author(s): W. Wagner
- Abstract
- Presentation
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Lung Cancer – What media can/should do Oncology today is one of the main topics of health/medicine media coverage. With the advent of targeted and immunotherapies there’s been a shift towards presenting the rapid advances in this field. But contrary to topics like skin cancer, breast and colorectal cancer lung cancer has stayed in the shadows of reporting until now. It has all been anti tobacco campaigns often regarding smokers immoral, stigmatizing the patients. Late diagnosis and advanced disease plus bad prognosis have not made lung carcinoma a hot topic – and patient advocacy groups, often key players in getting topics into the broad public, are rare. What we have to do (besides non smoking campaigns): Produce valid information on the developing field of early diagnosis (in risk groups). Inform about advancing science and medical procedures to overcome this old nihilistic view of lung cancer as something too poor and bad to speak and write about.
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Author of
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.05 - First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7 (ID 5347)
14:20 - 15:50 | Author(s): M. Boyer
- Abstract
- Presentation
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting.
Methods:
LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ~250 PFS events. The primary OS analysis was planned after ~213 OS events and a follow-up period of ≥32 months.
Results:
319 patients were randomised (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.
Conclusion:
Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-044 - Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7 (ID 5327)
14:30 - 15:45 | Author(s): M. Boyer
- Abstract
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7 trial, afatinib significantly improved median progression-free survival (PFS; HR=0.73 [95% CI, 0.57–0.95], p=0.017), objective response rate (70% vs 56%, p=0.008) and time to treatment failure (TTF; HR=0.73 [95% CI, 0.58–0.92], p=0.007) versus gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated the efficacy and safety of afatinib versus gefitinib in patients aged ≥75 years in a subgroup analysis of LUX-Lung 7 (NCT01466660).
Methods:
Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral afatinib (40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS and adverse events (AEs) by age (≥75/<75 years) were exploratory.
Results:
Of 319 patients randomised in LL7, 40 (13%) were aged ≥75 years (afatinib n=19, gefitinib n=21). Median PFS for both age groups was in line with the overall population and favoured afatinib versus gefitinib (patients ≥75 years: 14.7 vs 10.8 months, HR=0.69 [95% CI, 0.33–1.44]; patients <75 years: 11.0 vs 10.9 months, HR=0.76 [95% CI, 0.58–1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs (all grade [grade 3]) with afatinib in the older patient subgroup were diarrhoea (89% [21%]), rash (63% [5%]), dry skin (37% [0%]), and decreased appetite (32% [0%]). Dose reduction/discontinuation of afatinib due to treatment-related AEs was required in 53%/16% and 40%/5% of the older and younger subgroup, respectively.
Conclusion:
A small subgroup of patients in the LUX-Lung 7 trial were ≥75 years old (13%). In exploratory subgroup analyses of patients aged ≥75 and <75 years old, advancing age did not adversely affect the PFS benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients. These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with EGFRm+ NSCLC.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-055 - Incidence and Grade of Pneumonitis in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Anti-PD-1 Antibodies (ID 4538)
14:30 - 15:45 | Author(s): M. Boyer
- Abstract
Background:
Advanced non-small cell lung cancers (NSCLC) can be treated with anti-PD1 (programmed cell death 1) antibodies. Anti-PD-1 therapy can lead to immune mediated adverse events. This study examines the incidence of pneumonitis, a potentially fatal complication, in patients with advanced NSCLC treated with anti-PD-1 antibodies at 3 large hospitals in Sydney, Australia.
Methods:
NSCLC patients commenced on pembrolizumab (2 mg/kg or 10 mg/kg Q3W) or nivolumab (3 mg/kg Q2W) were assessed for adverse events including pneumonitis. Patient demographics, treatment history and immune mediated complications were collected. Pneumonitis was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. Pneumonitis treatment and clinical outcomes were collected. Serial imaging was reviewed with a blinded radiologist.
Results:
A total of 104 patients between 2012 and 2016 were treated with anti-PD-1 therapy. Median age for included patients was 67. Fourteen (14%), 35 (34%), and 53 (51%) had anti-PD-1 as first, second, or third and subsequent line treatment respectively. Nine patients (9%) developed pneumonitis. Three patients (4%) developed grade 3 (G3) or higher pneumonitis including one patient (1%) that died due to pneumonitis. All patients with ≥G3 pneumonitis required hospital admission with one requiring admission to a high dependency unit. None of the patients with ≥G3 pneumonitis were retreated with anti-PD1 therapy. All patients with ≥G3 pneumonitis died within 5 weeks of their diagnosis of pneumonitis. Seven patients with pneumonitis were treated with steroids. The median length of treatment with steroid was 29 days. Pneumonitis involved both lungs in 3 patients. Of the remaining 6 patients – 2 had all right lung lobes involved, 2 had two lobes and 1 had one lobe. Fifteen (14%) patients had a history of receiving concurrent chemoradiotherapy prior to anti-PD-1 therapy. A further 6 (6%) had curative intent radiotherapy and 15 (14%) had palliative radiotherapy to the thorax prior to anti-PD1 therapy. One of the patient with G3 pneumonitis had previously received radiotherapy to the chest. No association between prior radiotherapy and pneumonitis was seen.
Conclusion:
The incidence of pneumonitis is rare but our real-life multi-institutional experience demonstrates an incidence higher than reported in the literature. This complication can be life threatening and onset of ≥G3 pneumonitis is associated with short survival.
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PL04a - Plenary Session: Immune Checkpoint Inhibitors in Advanced NSCLC (ID 430)
- Event: WCLC 2016
- Type: Plenary
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:J. Soria, C. Zhou
- Coordinates: 12/07/2016, 08:45 - 09:40, Hall D (Plenary Hall)
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PL04a.05 - Discussant for PL04a.01, PL04a.02, PL04a.03, PL04a.04 (ID 7158)
08:45 - 09:40 | Author(s): M. Boyer
- Abstract
- Presentation
Abstract not provided
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SC26 - Angiogenesis Inhibition: Advances & Perspectives (ID 350)
- Event: WCLC 2016
- Type: Science Session
- Track: Biology/Pathology
- Presentations: 1
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SC26.02 - Angiogenesis Inhibition in Lung Cancer: Recent Advances and Perspectives (ID 6710)
11:00 - 12:30 | Author(s): M. Boyer
- Abstract
- Presentation
Abstract:
Angiogenesis is an important process in the development and progression of tumours. Across a range of tumour types markers of angiogenesis, such as elevated VEGF levels or increased micro vessel density, have been shown to be associated with poorer patient outcomes. The recognition that VEGF mediated signalling is a key driver of angiogenesis within tumours led to the development of a range of anti-angiogenic approaches targeting this biological process. These approaches have included monoclonal antibodies (bevacizumab, ramucirumab), decoy receptors (aflibercept), and receptor tyrosine kinase inhibitors (nintedanib, sorafenib, sunitinib, motesanib, vandetanib, cediranib, pazopanib), all of which have been evaluated in lung cancer. Despite this volume of clinical research, only three of these agents have been shown to produce benefit in patients with advanced non-small cell lung cancer (NSCLC): bevacizumab, ramucirumab and nintedanib. No antiangiogenic agent has to date been shown to be of benefit in small cell lung cancer. Bevacizumab, an anti-VEGF monoclonal antibody, was the first antiangiogenic therapy to be evaluated in NSCLC. Early studies identified that patients with squamous cancers were at risk of increased toxicity due to haemorrhage so randomised trials have been restricted to patients with non-squamous tumours. The ECOG 4599 randomized trial evaluated treatment with carboplatin and paclitaxel with or without bevacizumab[1]. In this study, as in most other studies of antiangiogenics, bevacizumab was continued in a maintenance phase following the conclusion of chemotherapy. The study demonstrated an improvement in overall survival (HR 0.79, 95% CI 0.67 – 0.92 p = 0.003). A second phase 3 study, AVAiL, evaluated the addition of two different doses of bevacizumab to the combination of gemcitabine and cisplatin, in a double blind manner[2]. The study demonstrated an improvement in progression free survival, but with no difference in overall survival. Based on the results of these two trials, bevacizumab received approval in several jurisdictions, but there remained some doubts over the benefit to patients given the lack of a confirmatory trial showing improved overall survival. A recent meta-analysis[3] incorporating these and other randomised studies has shown that bevacizumab produces a modest, but statistically significant improvement in overall survival (HR 0.90, 95% CI 0.81 – 0.99; p=0.03). Subsequently, a further randomised trial, BEYOND[4], has been published, with bevacizumab added to the combination of carboplatin and paclitaxel in a purely Asian population. This trial showed an improvement in overall survival (HR 0.68, 95% CI 0.50 – 0.93 p=0.015), with median OS increasing from 17.7 to 24.3 months. Bevacizumab has also been evaluated in the second line setting in combination with erlotinib (in patients unselected for EGFR mutations), without significant impact on overall survival in the BeTa study[5]. Ramucirumab is a monoclonal antibody directed against the VEGFR2 receptor. It has been evaluated in a randomised trial in the second line setting. Patients were randomised to receive treatment with docetaxel with or without ramucirumab[6]. Treatment was continued till progression, with monotherapy ramucirumab continued if toxicity developed to docetaxel (and vice versa). The primary endpoint of the study was overall survival, and the results indicated an improvement in overall survival for patients receiving ramucirumab (HR 0.86, 95% CI 0.75 – 0.98; p=0.023), with median survival increasing from 9.1 to 10.5 months. By contrast to the various studies of bevacizumab, this study included patients with squamous cell cancer, as well as those with non-squamous tumours, with the magnitude of benefit being similar in both histologic types. Addition of ramucirumab resulted in an increase in toxicity, with more hypertension, bleeding, and febrile neutropenia. However the rate of serious adverse events and of deaths due to adverse events were similar between the two study arms. The results of this study led to the approval of ramucirumab for patients with previously treated in NSCLC in some parts of the world, including the USA and Europe. However, subsequently, the results of trials of immune checkpoint inhibitors in the same patient population has resulted in many of these patients not receiving docetaxel chemotherapy, making it difficult to assess the appropriate role for this agent. The addition of a tyrosine kinase inhibitor to chemotherapy has been evaluated extensively in patients with advanced NSCLC in both the first and second line settings. The results of these trials have been disappointing, with none of them demonstrating an overall survival benefit. Many, however, did show some improvement in progression free survival. Only one of these agents, nintedanib, is approved (in Europe) for the treatment of patients with NSCLC. This is based on the results of the LUME-1 study, which compared treatment with docetaxel alone with docetaxel plus nintedanib in patients with previously treated NSCLC[7]. In this study, progression free survival (the primary endpoint) was longer with the addition of nintedanib (3.4 vs. 2.7 months, HR 0.79, 95% CI 0.68 – 0.92; p=0.0019). Although there was no difference in overall survival in the whole study population, in the predefined subset of patients with adenocarcinoma and progression within 9 months of initial therapy median overall survival increased from 7.9 to 10.9 months (HR 0.75, 95% CI 0.60 – 0.92; p=0.007). Similar, though less extreme results occurred in all patients with adenocarcinoma. There was no effect on survival of patients with squamous histology. The combination resulted in an increase in the rate of adverse events, predominantly diarrhoea, liver function abnormalities and vomiting. To date, no biomarker of angiogenesis that allows the selection of patients for treatment with has been identified. As a consequence, patient selection (for bevacizumab) is based on the avoidance of toxicity, by excluding groups of patients known to be at higher risk (e.g. those with squamous cell histology, or a history of haemoptysis). Furthermore the inability to identify those patients most likely to benefit, along with the relatively small improvements in survival means that from an economic viewpoint, the cost per life year gained is high. This has resulted in antiangiogenics not being widely used in some countries. References 1. Paclitaxel Carboplatin alone or with bevacizumab for non-small-cell lung cancer. Sandler et al. N Engl J Med 2006; 355: 2542 – 2550 2. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for non-squamous non-small-cell lung caner: AVAiL. Reck et al. J Clin Oncol 2009; 27: 1227 – 1234 3.Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum based chemotherapy as first-line treatment in patients with advanced non-small cell lung cancer. Soria et al. Ann Oncol 2013; 24: 20 – 30. 4. BEYOND: A randomized, double-blind, placebo-controlled, multicentre phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent non-squamous non-cell lung cancer. Zhou et al. J Clin Oncol 2015; 33: 2197 – 2204 5. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind placebo-controlled phase 3 trial. Herbst et al. Lancet 2011; 377: 1846 – 1854 6. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre double-blind randomised phase 3 trial. Lancet 2014; 384: 665 – 673 7. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-1): a phase 3 double blind , randomised controlled trial. Reck et al. Lancet Oncol 2014; 15: 143- 155
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