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J.S. Lee

Moderator of

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    SC23 - The Importance of Co-Operative Groups (ID 347)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 6
    • Now Available
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      SC23.01 - Cooperative Groups in Latin America (Now Available) (ID 6694)

      C. Mathias

      • Abstract
      • Presentation
      • Slides

      Abstract:
      More than 100 million people in Latin America will be > 60 years of age by 2020. Age, smoke exposure and infectious causes of cancer (HPV, Hepatitis B, and H. pylori) will continue to drive the burden of cancer in the region. Cancer mortality rates in Latin America are approximately twice those of the United States (1). Until not so long ago, drug development and cancer clinical research were conducted almost exclusively in wealthy developed regions of the world. However, over the last 2 or 3 decades, clinical trials have been progressively incorporated in a challenging globalization process. As such, the conduct of trials in a global scale represents a major aspect to be taken into account when analyzing the future development of the area. The globalization of clinical trials, as well as multinational and multi-institutional research collaboration, represents a scenario that requires permanent and concentrated efforts by all involved if we are to achieve the fundamental objective of generating the appropriate answers to the health problems we face around the world (2). Up to the 1980s, North American and European cooperative groups mostly sponsored by the National Cancer Institute (NCI) conducted most of the pivotal practice changing trials. At that time, a progressive shift in the funding of research toward pharmaceutical companies was seen. In parallel, an increasing participation of research sites from countries outside North America and Western Europe was identifıed and has since transformed the development of new medications to what is now an increasingly globalized process (2). The number of registered clinical trials has increased in all geographic regions during this time period, with the average annual growth greatest in the Asian (30%) and Latin American/ Caribbean (12%) regions (3). Early trials seem to be conducted more frequently in North America (62%), whereas confırmatory trials are more frequent in Eastern Europe, Latin America, and Asia (4). Data from ClinicalTrials.gov shows that over 70% of the registered cancer phase I trials are conducted in the United States, whereas less than 1% are conducted in Latin America. In larger registered phase III studies, 40% are conducted in the United States, 43% in Western Europe, and 17% in Latin America (5). Involvement of investigators from developing countries in the planning phases of the trial is essential as they may provide valuable contribution while being exposed to an experience that will have long lasting effects in the future development of regional studies. Other than addressing a question that interests a pharmaceutical company, developing a reliable research infrastructure and local expertise allow researchers to expect the development of locally coordinated research addressing pertinent regional health questions benefıting the local community. As quality is a fundamental principle in the conduct of clinical research, we need to address monitoring, auditing, and inspections as a basic element in the process of globalization. In recent years, a number of independent research groups have been created in Latin America: The Chilean Cooperative Group for Oncological Research (Grupo Oncológico Cooperative Chileno de Investigación, or GOCCHI) is a nonprofit corporation registered in Chile since 1998. GOCCHI is conducting academic clinical trials in oncology based on the highest scientific, methodologic, and ethical standards (http://www.gocchi.org). The Peruvian Oncology Clinical Studies Group (Grupo de Estudios Clínicos Oncológicos Peruano, or GECOPERU) was founded in March 2005 as a nonprofit academic and research organization. It has a central operating office and partnerships with several international groups (CIBOMA, IBCSG, BIG, and others) (http://www.gecoperu.pe). Founded in 2007, the Argentine Group for Clinical Research in Oncology (Grupo Argentino de Investigación Clínica en Oncología, or GAICO [is composed of 15 cooperating groups and includes various health professionals from public and private institutions (www.gaico.org.ar). The Latin American Cooperative Oncology Group (LACOG) was founded in 2008 by medical oncologists from several Latin American countries that has developed a network of investigators in oncology for epidemiologic and clinical studies in cancer. LACOG has 47 members in 39 sites from 10 countries in the region. Currently, the group has several ongoing studies. The Brazilian Group of Thoracic Oncology (GBOT) is currently hosted at LACOG and is involved in some research initiatives (www.lacog.org.br) (www.gbot.med.br). CLICaP (Latin American Consortium for Lung Cancer Research) This consortium was created in 2010 to develop collaborative studies on the biology, diagnosis and treatment of lung cancer. CLICaP has published over 20 studies involving participants from Mexico, Costa Rica, Panama, Venezuela, Colombia, Ecuador, Peru, Chile, Argentina and Uruguay. Some of this work has established genomic differences between populations for mutations in EGFR, KRAS and ALK ROS1 following analysis of over 8500 samples (7). There are several challenges of research in South America including costs (6), regulatory issues and difficulty in recruitment but there also several advantages of performing trials in developing countries such as availability of patients, lower costs and faster accrual. As an added and very important characteristic, patients enrolled in developing countries are more frequently treatment-naive and have less, or many times, no competing trials as alternative (8) As more trials are conducted in resource-limited settings, good clinical practices and ethical assurances must be secured. Human participation in clinical research is essential to advance medicine and public health, and expanding clinical trials mandates constant oversight to ensure research quality and protection of study subjects. Some decades ago, the development of global clinical research could have been considered a dream; it is now a pressing need that should be considered unavoidable in the future (2). References: 1 Goss, P; Lee, BL; Badovinac-Crnjevic, T et al. Planning Cancer Control in Latin America and the Caribbean. Lancet Oncol 2013; 14: 391–436 2 Barrios, C; Werutsky, G and Martinez-Mesa, J. The Global Conduct of Cancer Clinical Trials: Challenges and Opportunities. ASCO Educational Book, e132- e139, 2015 3 Drain PK, Robine M, Holmes KK, et al. Trail watch: global migration of clinical trials. Nat Rev Drug Discov. 2014;13:166-167 
 4 Thiers FA, Sinskey AJ, Ernst R. Trends in the globalization of clinical trials. Nature Reviews Drug Discovery. 2008;7:13-14. 
 5 www.clinicaltrials.gov 6 Kaitin KI. The Landscape for pharmaceutical innovation: drivers of 
cost- effective clinical research. Pharm Outsourcing. 2010;2010: 
3605. 
 7 Rolfo C, Caglevic C, Bretel B et al. Cancer clinical research in Latin America: current situation and opportunities. Expert opinion from the first ESMO workshop on clinical trials, Lima, 2015. ESMO Open 2016;1 8 Smith WT. FDA requires foreign clinical studies be in accordance with 
good clinical practices to better protect human subjects. ABA Health 
eSource. 2008; 5:1-3. 


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      SC23.02 - Co-Operative Groups in Europe: Lessons Learned and Perspectives (Now Available) (ID 6695)

      S. Peters

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC23.03 - How Could High-Volume Centers in Developing Countries Access Cooperative Group Trials? (Now Available) (ID 6696)

      U. Yılmaz

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung cancer has the second highest absolute incidence globally as well as in developing countries and ranks fourth in developed countries. It is the most common cause of cancer death by absolute cases globally as well as in developing and developed regions. The economic burden of lung cancer care is highest relative to other cancers in the European Union. Research is at the core of achieving improved outcomes from cancer, be it in defining country-specific epidemiology of the disease, understanding the pathogenesis of disease, identifying new targets for therapeutic agents, or directing policy to achieve affordable and equitable outcomes. Cancer researchs are one of the most globally active domains of science, with more than $14 billion per annum. A critical part of the health research portfolio is the testing of interventions through randomized controlled trials. Trials can range from highly controlled explanatory trials through to pragmatic trials of new health technologies and models of service delivery. Recruitment problems also have practical and financial impacts, as they can delay completion of research or reduce its timely impact on patient health and wellbeing. Achieving appropriate levels of patient and professional participation has been a significant obstacle to evidence-based practice. Published data show that the minority of trials recruit successfully, either in terms of reaching their planned sample size, or delivering the planned sample in the expected recruitment window Despite all the diffuculties, clinical trials have become increasingly globalized due to the inclusion of more non-traditional locations, especially those in central and eastern Europe, Latin America, and Asia. The increased globalization of clinical research has arisen for several reasons, but primarily due to the need for faster and more economically efficient studies. Moves towards standardizing and harmonizing clinical research practices have facilitated the rise of globalized clinical research. However, the expansion of multinational clinical research peaked in 2009, which could reflect that the large-scale expansion of multinational clinical research effort has reached its global capacity. When the distribution of multinational clinical trials is examined after being stratified according to the condition or disease, lung cancer is not among the five most frequently studied conditions apart from Asia. The results of a bibliometric analysis of global research on lung cancer between 2004-2013 in the 24 leading countries in cancer research showed that despite a doubling of the volume of lung cancer research worldwide between 2004 and 2013, it still only accounts for a small proportion of the overall oncology research publication output (5.6%). In fact, the relative commitment (RC) to lung cancer research compared with that to total oncology research output has fallen in most countries during this period, including in the 23 countries with exception of the China. Turkey, Poland, Canada, Greece, and the United States, despite having the highest country-specific burden of lung cancer, have all seen a decrease in their RC to lung cancer research. Research from Norway, Austria, Switzerland, Belgium, and Sweden had the highest proportion of international contributors . By comparison, relative to their research output, the East Asian countries (Taiwan, India, the Republic of Korea, and Japan) and Turkey had the least amount of international collaboration. With regard to multinational studies, only 1.2% of articles had collaborators from five or more countries and 0.3% from 10 or more countries. The aim of co-operative groups in oncology is to perform multi-center clinical trials for cancer research. Research results are often conveyed to the worldwide medical community through scientific publications. In order to complete the trials within the period specified, it is obvious the need of the qualified and high-volume cancer centers. The barriers to participation of high-volume hospitals in the cooperative group trials should be determined and eliminated. Since the 1970s, centers for thoracic diseases that emerged from former tuberculosis hospitals, particularly in Europe, have focused on the diagnosis and treatment of patients with lung cancer. Traditionally, these centers were staffed by pulmonologists and thoracic surgeons, but now include an extended range of health care workers including the disciplines of radiation oncology, medical oncology, palliative care and rehabilitation medicine. These high-volume centers treat all aspects of problems affecting patients with lung cancer. In 2010, the hospitals with a median 400 new patients per year were in Albania, Belarus, Bulgaria, the Czech Republic, Poland, Romania and Slovenia. The hospitals with more than 1000 new patients with lung cancer per year were in Poland, Bulgaria, Croatia, Turkey. We have to foster the cooperative study groups in lung cancer to provide collaboration between study group and these hospitals. High-volume hospitals should be identified and hospital-based representatives should be determined. Supreme organisations as European Thoracic Oncology Platform providing collaboration among study groups and hospitals, should be able to invite the high-volume hospitals with site evaluation. These high-volume centers have to review whether adequately equipped and set up or not for participation in research projects and clinical trials. References 1- Gaga M. An Official American Thoracic Society/European Respiratory Society Statement: The role of the pulmonologist in the diagnosis and management of lung cancer. Am J Respir Crit Care Med 2013; 188(4): 503-7. 2- Blum T. G. The European initiative for quality management in lung cancer care. Eur Respir J. 2014; 43: 1254-77 3- Loddenkemper R, 100 years DGP-100 years of pneumology in Germany. Pneumologie 2010; 64:7-17. 4- Richter TA. Clinical research: A globalized network. PLoS ONE 2014; 9(12): 1-12 5- Aggarwal A. The state of lung cancer research: A global analysis. J Thorac Oncol 2016; 11(7): 1040-50

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      SC23.04 - Cooperative Groups in China: The CSCO Experience (Now Available) (ID 6697)

      Q. Zhou

      • Abstract
      • Presentation
      • Slides

      Abstract:
      In order to keep up with the rapid development of world cancer treatment exploring, Chinese clinical oncology professionals, relevant enterprises and public institutions voluntarily constituted a non-profit professional academic group which is known as The Chinese Society of Clinical Oncology (CSCO) in April 1997. The CSCO organization not only pay attention to international collaboration such as establishing reciprocal memberships with American Society of Clinical Oncology (ASCO) , European Society for Medical Oncology (ESMO), Clinical Oncological Society of Australia (COSA) and participating rotation of presidency organization of Asia Clinical Oncology Society (ACOS), but also committed to Chinese Oncology development. The CSCO annual meeting delivered the latest advancements and research fruit from home and abroad which offered a great academic exchange platform for vast amount of Chinese oncologists. CSCO also organize experts to make tumor diagnosis and treatment standardized guideline. Up to date, CSCO has launched dozens of guidelines regarding many major cancers in china, including non-small cell lung cancer, colorectal cancer and hepatocellular carcinoma. The newly made guideline about non-small cell lung cancer has fully considered Chinese special situation, not only disease characteristics, but also social economic factors, which made a good example of better suiting Chinese oncologists and patients. Other than this, CSCO developed multi-center clinical researches which offered solid evidence for Chinese cancer patients and made contribution to world cancer diagnosis and treatment. Most of clinical researches were carried out by Study Group majored in different cancers, such as Chinese Thoracic Oncology Group (CTONG), Chinese Breast Cancer Study Group (CBCSG) and Chinese Gastrointestinal Oncology Group (CGOG). The CSCO also keeps an open mind and follows the trend of hot spot, such as building expert committee on cancer biomarkers and precise medicine, even making consensus on standard of driver gene mutation test, standard of operation procedure and so on. Of all the Study Groups in CSCO, CTONG is the most active and fruitful committee. CTONG is also the most active organization in lung cancer field in China. Through the great effort of four top experts majored in lung cancer (Yi-Long Wu, Li Zhang, Shun Lu and Cai-Cun Zhou), CTONG was successfully established in 2007. With the goal of designing and developing multi-center clinical trials in the field of chest tumor, especially for lung cancer, providing high level of evidence for clinical practice of thoracic tumor, promoting standardization, modernization and internationalization of clinical and research work in thoracic tumor area and finally improving the level of diagnosis and treatment of chest tumor in China, as well as international status, CTONG has actually made massive efforts and achieved great success. Up to date, CTONG has 31 members from 15 provinces and municipality cities and has successfully performed 47 clinical trials in China. Half of these clinical trials established China lung cancer treatment modalities. Take CTONG 0802 study (OPTIMAL) for example, the multicenter open-label randomized phase II study compared erlotinib with combination of gemcitabine and cisplatin in first-line treatment of patients with EGFR mutation-positive NSCLC[1], Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs no patients with either event on erlotinib), which suggested that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. The results of CTONG0802 was orally presented on ESMO2010, WCLC 2011, discussed on ASCO 2011 and published on Lancet Oncology. CTONG 0901 study compared erlotinib with gefitinib in patients with EGFR mutation positive stage IIIb/IV NSCLC and found no PFS or OS difference between these two regimens which offered solid evidence for clinical choice[2]. CTONG also paid attention to first-line maintenance therapy, second-line treatment, Another well-known study of CTONG is FASTACT-II (CTONG0902) proved that erlotinib maintenance therapy after first-line gemcitabine combined with cisplatin improves overall survival of stage IIIB/IV NSCLC patients[3]. CTONG 0806 study suggested improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced non-squamous NSCLC[4]. There were also many studies focused on palliative treatment, brain metastasis and peri-operative treatments and achieved meaningful results in these fields. Additionally, CTONG has initiated the very first real-world study in China targeting 1st line treatment pattern of advanced non-squamous NSCLC patients, the study concern difference between scientific achievements and clinical practice in China and set a great beginning of caring for patients’ actual profits. The currently ongoing reform for new drug approval of CFDA provides great chances for the development of clinical trials in China and domestic drug innovation such as icotinib and apatinib. CTONG and other study groups also face more opportunities. CTONG, as the successful example of CSCO study groups, is expected to make more contributions to china lung cancer treatment. Hopefully, CSCO achievements will finally benefit more Chinese cancer patients and make more contribution to world cancer control. Reference: 1. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735-742. 2. Yang JJ, Zhou Q, Yan HH, et al. A Randomized Controlled Trial of Erlotinib versus Gefitinib in Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations (CTONG0901). J Thorac Oncol 2015;10(2), S321(ABSTRACT MINI 16.03) 3. Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. 4. Zhou Q, Cheng Y, Yang JJ, et al. Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial. Ann Oncol. 2014 ;25(12):2385-2391.

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      SC23.05 - Co-Operative Groups in North America (Now Available) (ID 6698)

      S. Malik

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC23.06 - Challenges and Costs of Cooperative Group Trials (Now Available) (ID 6699)

      T. Brodowicz

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    P1.03 - Poster Session with Presenters Present (ID 455)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
    • Now Available
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      P1.03-039 - Is It Necessary to Repeat Lung Cancer Screening with Low-Dose CT(LDCT) in Female Never Smokers? (Now Available) (ID 4422)

      J.S. Lee

      • Abstract
      • Slides

      Background:
      Lung cancer (LC) screening is not recommended for low-risk subjects, including never smokers. However, LDCT is often performed in Korea as a part of cancer screening program even for healthy female never smokers (FNS). To examine the role of LDCT screening in FNS, we estimated the risk of subsequent development of LC according to their initial LDCT findings and age groups.

      Methods:
      This retrospective cohort study included FNS aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database (Dec 2013) and vital status (Dec 2014) from Statistics Korea. LDCT findings were reviewed using Lung Imaging Reporting and Data System (Lung-RADS). LC risk and outcomes were analyzed according to initial LDCT findings and age groups using the national data up to 12 years after the LDCT. .

      Results:
      There were 4,365 FNS with mean age of 51.1±7.6 years (median F/U time = 9.7 years). Overall, twenty-two LCs (0.5%) were identified with an incidence rate of 52.58 (95% CI 34.62-79.86) per 100,000 person-years. The incidence rates were 8.53 (2.75-26.44), 75.16 (24.24-233.04), 0 and 1665.58 (1020.38-2718.72) in subjects with category 1, 2, 3 and 4, respectively. The cumulative incidence is shown in Fig 1. The incidence rates were 35.30 (95% CI 18.99-65.00) and 88.84 (50.45-156.44) in age with 40~54 years and 55~79, respectively. Three women among 16 classified into category 4 died of LC, while no death in those with category 1 , 2, or 3 [median time to LC diagnosis= 5.1 years (range, 2.8-8.8)]. Fig 1. Cumulative incidence of lung cancer according to lung-RADS Figure 1



      Conclusion:
      Although, the effectiveness of lung cancer screening is in FNS still unclear, repeat LDCT seems to be unnecessary in those with category 1, 2 and 3, at least within 5 years after initial LDCT.

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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
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      P3.02b-126 - Clinical Activity of Olmutinib (HM61713) Used on a Compassionate IND Basis for Patients with Lung Adenocarcinoma (LADC) in Korea (ID 5605)

      J.S. Lee

      • Abstract

      Background:
      Olmutinib (HM61713) is an oral EGFR tyrosine kinase inhibitor (TKI), which selectively inhibits EGFR mutations, including both activating mutations and T790M, but not EGFR wild-type. It showed good safety profile and promising anti-tumor activity in patients with EGFR mutated NSCLC that progressed after EGFR-TKIs, especially in those with T790M mutation.

      Methods:
      Between 08/2014 and 05/2016, we treated 27 LADC patients (11 male, 16 female) with Olmutinib on a compassionate IND basis, which was provided by Hanmi Pharmaceutical Co. Ltd. The starting dose of oral Olmutinib was 650 mg/day in 12 patients and 800 mg/day in 15 patients. The EGFR mutation status was assessed either by direct sequencing after PCR or by PNA mediated real-time PCR clamping or both, and ddPCR of cell-free plasma DNA. Tumor response was assessed using RECICT criteria every 2-3 cycles of treatment with repeat CT chest, MRI brain, and PET/CT, as appropriate.

      Results:
      The median age was 62 years (range 42-74); ECOG was 0/1/2/3 in 6/12/7/2 patients. All but one patient had prior treatment with EGFR-TKIs (17 as first[t]-line therapy, 9 upon PD after chemotherapy). In 5 patients, EGFR-TKI was the only treatment given before Olmutinib while 21 patients received median of 2 (range 1-5) chemotherapy regimens in addition (18 platinum-based, 3 non-platinum-based). Prior EGFR-TKIs used were gefitinib in 14, erlotinib in 10, and both in 2 patients; 2 patients received afatinib in addition. Overall, 15 of 27 received 3 or more regimens of chemo and/or EGFR-TKI (median, 3; range, 0-7). While one patient had wild type EGFR only, 26 patients had EGFR mutations. One patient had de novo EGFR T790M mutation in resected tumor sample, and 14 had Ex19 del, 9 had L858R mutation, 1 had both Ex19 del & L858R and 1 had Ex 20 P772S mutation. T790M mutation was detected in 18, not detected in 7, and unknown in 2 patients. Of 24 patients evaluable for tumor response, 14(58.3%) achieved PR, 2 SD, and 8 PD. Patients with T790M mutation tend to have better ORR than those without or unknown (12/16 [75.0%] vs. 2/6 [33.3%] vs. 0/2 [0.0%]). Olmutinib was well tolerated with no additional major adverse effects other than what was previously reported in phase I/II studies.

      Conclusion:
      Olmutinib showed promising anti-tumor activity for patients with EGFR mutated LADC that progressed after prior treatment with EGFR-TKIs, especially in those with T790M mutation, including the one who had de novo T790M mutation.

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    P3.06 - Poster Session with Presenters Present (ID 492)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Trial Design/Statistics
    • Presentations: 1
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      P3.06-007 - The Consequence of Incomplete Follow-up in Hospital-based Survival Study as Compared with National Vital Status-based Results (ID 5887)

      J.S. Lee

      • Abstract

      Background:
      Loss to follow-up (FU) is an important issue in survival analysis using the data based on hospital records. To better address the magnitude of this issue in a real clinical setting, we compared survival outcomes from hospital database with those from national cancer registry data which incorporated national vital status record.

      Methods:
      From the hospital database of National Cancer Center Hospital, Korea, we identified 970 small cell lung cancer (SCLC) patients who were treated between 04/2001 and 04/2013. Most of them were male (n = 854) and smokers (n = 906). Median age was 63 years (range, 32–80 years). We made two survival datasets, hospital-based dataset (HD) and cancer registry-based dataset (CD).

      Results:
      Of 352 LD-SCLC patients, there were 144 deaths in the HD and 107 additional deaths were identified in the CD (Total= 251). There was no difference in median progression free survival (PFS) between the HD and CD (12.7 months [95% CI, 10.9-14.6] vs. 12.3 months [95% CI, 10.8-14.2]). But, median OS in the HD was significantly longer than in the CD (55.7 months [95% CI, 35.8-115.6] vs. 26.3 months [95% CI, 22.8-30.8]). The 5-year survival rate of LD-SCLC was 48.7% vs. 29.6% in the HD and CD, respectively. For 618 ED-SCLC patients, there were 234 deaths in the HD while 341 additional deaths were confirmed in the CD (Total= 575). Median PFS from the HD was similar to that from the CD (6.5 months [95% CI, 6.2-6.9] vs. 6.4 months [95% CI, 6.1-6.8]). Median OS of HD was 14.5 months [95% CI, 13.5-16.9], significantly longer than that of CD (11.9 months [95% CI, 11.2-12.9]). The 5-year survival rate of ED-SCLC in the HD and CD was 11.5% and 3.5%, respectively. In the simulation analysis, the estimated median OS increased as the proportion of patients who were actually dead but censored in the HD increased. When this proportion was 25%, 50% and 75%, the estimated median OS was 27.8 months, 33.8 months, and 37.2 months for LD-SCLC, respectively, and 12.5 months, 13.1 months, and 13.7 months for ED-SCLC. Obviously, this discrepancy reflects the limitation of HD-based survival analysis since medical records do not trace all patients until death, especially for those who did not return for subsequent follow-up care.

      Conclusion:
      Incomplete follow-up, by increasing the number of censoring events, could result in spurious prolongation of overall survival, which warrants caution in interpreting the HD-based survival analysis.

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    YI01a - Clinical Trials & Scientific Mentoring (ID 414)

    • Event: WCLC 2016
    • Type: Young Investigator Session
    • Track: WCLC 2016
    • Presentations: 1
    • Now Available
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      YI01a.04 - Critical Eye on Practice Changing Literature (Now Available) (ID 6738)

      J.S. Lee

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Clinical trials in cancer have typically investigated agents or regimens in selected groups of patients based primarily on histology and clinical characteristics (e.g., tumor stage, performance status, prior treatment, etc). The major goal of those trials was to demonstrate statistically significant improvement in outcome with minimum p-value of 0.05, as compared with the control arm. In the majority of cases, this approach resulted in only small incremental improvements in overall survival. In some cases, even without any improvement in survival, a certain regimen became the foundation for adding novel targeted agents only based on the favorable toxicity profile and has been widely used in practice over the last two decades. More recently, targeted therapies administered to patients with biologically relevant biomarkers, such as activating EGFR mutations and ALK alternation, have produced substantial improvements in outcomes and rapidly changed the treatment paradigm of lung cancer. In addition, newer treatment modalities such as immune check-point inhibitors and antibody-drug conjugates are emerging as highly effective therapies that are providing improvements in patient outcome. In fact, between 2004 and 2015, 14 new drugs were approved by the FDA for NSCLC. However, the relevance of statistical significance has increasingly been challenged when the treatment effect is small. [1,2] To resolve this issue, there has been growing consensus to raise the bar of efficacy for approving new cancer drugs.[3,4] The critical question is what is clinically meaningful and how can this outcome be measured. The FDA considered OS to be the standard clinical benefit endpoint that should be used to establish efficacy of a treatment in patients with locally advanced or metastatic NSCLC.[5] The FDA also has recognized that PFS may be appropriate as the primary endpoint to establish efficacy for drug approval if the trial is designed to demonstrate a large magnitude for the treatment effect as measured by both the hazard ratio and absolute difference in median PFS and an acceptable risk-benefit profile of the drug is demonstrated. The remaining question is, “What is clinically meaningful?” Modest benefits could be considered worthwhile if associated with moderate costs and toxicity, whereas a new drug with a very high cost and/or substantial toxicity is worthwhile only if it produces sizeable clinical benefits. To address this issue, the ASCO Cancer Research Committee convened four disease-specific working groups, including the lung cancer working group. The Committee generally agreed that relative improvements in median OS of at least 20% are necessary to define a clinically meaningful improvement in outcome.[3] For lung cancer, it was recommended that one experimental agent in non-squamous NSCLC should be considered practice changing if it increases PFS by at least 4 months and OS by 3.5-4 months with a corresponding death risk reduction of 20-24%. Due to less favorable prognosis, the desired benefit in squamous NSCLC was 3 months increase in PFS and 2.5-3 months increase in OS with a death risk reduction of 20-23%.[3] Obviously, if a new treatment is to be introduced into clinical practice, it is not sufficient to demonstrate that it is "better than” or “non- interior to” the standard therapy. As cancer care costs continue to increase at an unsustainable rate, oncology professionals need to focus more on delivering value-based patient care rather than simply practicing evidence-based patient care. In addition, it has become increasingly clear that the traditional fee-for-service model will no longer serve the interest of all the parties involved, including the pharmaceutical company.[6] It seems to be a matter of time that the fee-for-service system will be replaced with the value-based reimbursement system. Reference 1. Sobrero A, Bruzzi P. Incremental advance or seismic shift? the need to raise the bar of efficacy for drug approval. J Clin Oncol 2009;27:5868–73. 2. Ocana A, Tannock IF. When are "positive" clinical trials in oncology truly positive? J Natl Cancer Inst 2011;103:16–20. 3. Ellis LM, Bernstein DS, Voest EE, Berlin JD, Sargent DJ, Cortazar P, et al. American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol 2014;32:1277–80. 4. Sobrero AF, Pastorino A, Sargent DJ, Bruzzi P. Raising the bar for antineoplastic agents: How to choose threshold values for superiority trials in advanced solid tumors. Clin Cancer Res. 2015;21:1036-43. 5. United States, Department of Health and Human Services, Food and Drug Administration (FDA). Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics Guidance for Industry (published April 2015) : Available online: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM259421.pdf, 2015. 6. Eaton KD, Jagels B, Martins RG. Value-based care in lung cancer. Oncologist. 2016;21:903-6.

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