T here are currently no approved biomarkers to identify patients with non- small cell lung cancer (NSCLC) who are more likely to respond to immunochemotherapy. The Spanish Lung Cancer Group found that low levels of circulating tumor DNA (ctDNA) before treatment is a strong prognostic marker for both progression-free survival (PFS) and overall survival (OS) in patients with treatment-naïve stage IIIA NSCLC. “Pretreatment ctDNA levels can identify patients at high risk of progressing and death,” said Atocha Romero, MD, PhD, director, Medical Oncology Liquid Biopsy Laboratory, Hospital Universitario Puerta de Hierro- Majadahonda, Spain. “Circulating tumor DNA outperformed radiological responses assessed according to RECIST criteria in the prediction of survival.” Dr. Romero presented ctDNA findings from the NADIM trial during OA20: Exploring Treatment Modalities and Tools in Locally Advanced NSCLC. The phase II trial was one of the first to assess neoadjuvant immunochemotherapy in stage IIIA NSCLC. Neoadjuvant nivolumab plus chemotherapy, followed by surgery up to 1 year of adjuvant nivolumab, showed a 3-year OS of 81.9%, nearly 3 times historical rates. A total of 46 patients were enrolled in the single-arm, open-label study between April 26, 2017, and August 25, 2018, at 18 hospitals in Spain. CONQUERING THORACIC CANCERS WORLDWIDEPOST EDITION INSIDE: PAGE 3 Surgery for stage IIIA-N2 NSCLC PAGE 4 Access to surgery for operable MPM PAGE 4 ICIs, age, and stage IV NSCLC PAGE 3 PLCO model detection rates PAGES 7-14 In Case You Missed It: Recaps from key WCLC 2021 Sessions LURBINECTEDIN MAY BE MORE EFFECTIVE IN PATIENTS WITH PLATINUM-SENSITIVE SCLC AN EXPLORATORY ANALYSIS suggests that lurbinectedin may be more effective in patients with small cell lung cancer (SCLC) that is sensitive to platinum therapy. The indication of improved benefit came from a post hoc analysis of the trial that led to the accelerated approval of lurbinectedin. “Although the small sample size and exploratory nature of this analysis precludes any firm conclusion, these results indicate that lurbinectedin may extend the treatment-free interval in patients with platinum sensitive small cell cancer,” said Vivek Subbiah, MD, associate professor of investigational cancer therapeutics and medical director, Clinical Center for Targeted Therapy, University of Texas MD Anderson Cancer Center. Lurbinectedin was approved in July 2020 for metastatic SCLC in adults with progression on or after platinum-based chemotherapy. The accelerated approval followed a single-arm, open- label, phase II basket trial that showed an overall response rate (ORR) of 35.2%, median duration of response of 5.3 months, and overall survival (OS) of 9.3 months. Dr. Subbiah reported findings from a post hoc Atocha Romero, MD, PhD ... see LURBINECTEDIN on page 15 PRETREATMENT ctDNA SHOWS PROMISE AS A PROGNOSTIC MARKER IN STAGE IIIA NSCLC ... see PRETREATMENT on page 15 OUR COMMITMENT TO ONCOLOGY TODAY’S CLINICAL RESEARCH DEVELOPS HOPE FOR TOMORROW VV-OTHR-US-DEL-0521 04/2021 © Lilly USA, LLC 2021. All rights reserved. Efficacy with lurbinectedin Subsequent therapy (n = 47) No subsequent therapy (n = 58) All patients (n = 105) ORR, n (%)18 (38.3)19 (32.8)37 (35.2) Median DoR, months (95% CI)5.5 (2.9, 6.4)5.3 (3.5, 9.1)5.3 (4.1, 6.4) Median OS, months (95% CI)11.9 (7.6, 14.9)7.3 (4.3, 9.7)9.3 (6.3, 11.8) 12-month OS, % (95% CI)45.8 (30.7, 59.7)16.6 (4.7, 34.8)34.2 (23.2, 45.1) ORR, overall response rate; DoR, duration of response; OS, overall survival; CI, confidence interval; CTFI, chemotherapy-free interval. Efficacy of Lurbinectedin in Patients Who Received Subsequent Therapy, Including Patients With Platinum-sensitive Diseasea Efficacy with lurbinectedin CTFI ≥90 days (n = 15)b CTFI ≥180 days (n = 7)b CTFI <90 days (n = 2) Median OS, months (95% CI) 15.9 (6.3, 19.3) 17.7 (15.9, –) 10.1 (7.6, 12.6) 12-month OS, % (95% CI) 70.7 (46.5, 95.0) 100 (100, 100) 50.0 (0.6, 91.0) Efficacy with lurbinectedin among patients who received subsequent platinum-based therapy b Includes censored patients (alive at data cutoff) who received platinum (n = 4, n = 3) or platinum + I/O (n = 1; n =1) in the CTFI ≥90 and CTFI ≥180 groups, respectively. 48% 54% Platinum- based therapy n = 60 n = 20 n = 31 n = 13 n = 15 n = 7 52% 65% Subsequent systemic therapy Patients with platinum-sensitive diseaseb ≥90 days ≥180 days CTFI a Results from a post-hoc exploratory analysis. bPatientswith platinum-resistant disease (CTFI <90): n = 45; subsequent therapy, n = 16; platinum-based therapy, n = 2. Vivek Subbiah, MDLOCATION STUDY TREATMENTS KEY ELIGIBILITY CRITERIA ASIA, AUSTRALIA, NORTH AMERICA RANDOMIZED, PHASE 2, OPEN-LABEL •Zimberelimab (anti-PD-1 antibody) •Domvanalimab(anti-TIGIT antibody)+ Zimberelimab •Domvanalimab + Zimberelimab + Etrumadenant (dual adenosine A 2a /A 2b receptor antagonist) NSCLC: •Histologically confirmed squamous or nonsquamous •PD-L1 positive •Metastatic •No EGFR or ALK mutations These molecules and their uses are investigational, have not been proven to be safe and effective, and have not been approved by any health authority. ASIA, EUROPE, LATIN AMERICA RANDOMIZED, PHASE 3, OPEN-LABEL •Zimberelimab •Chemotherapy •Domvanalimab + Zimberelimab NSCLC: •Histologically confirmed squamous or nonsquamous •Treatment-naive •PD-L1 positive •Locally advanced or metastatic •No EGFR or ALK mutations Do you have patients with NSCLC who could benefit from participating in an EXPLORE THE STUDIES AT arcusbio.com/clinical-trials/lung-cancer HAVE A PATIENT TO REFER? email us at clinicaltrials@arcusbio.com today! Arcus Biosciences, a company focused on precision combinations for cancer, is currently enrolling: ALK= anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; NSCLC=non-small cell lung cancer; PD-1=programmed death protein 1; PD-L1=programmed death ligand 1; TIGIT=T cell immunoreceptor with immunoglobulin and ITIM domain. © 2021 Arcus Biosciences, Inc. All rights reserved. Approved July 2021. ANTI-TIGIT CLINICAL TRIAL?POST EDITION | WORLDWIDE VIRTUAL EVENT3 No dierences in Survival between Induction Chemotherapy and Induction Chemoradiation 0.00 0.25 0.50 0.75 1.00 O v era l l S ur v i v a l ( P r o b a b ili t y ) 2572221741359673 Induction Chemoradiation 2011741371027048 Induction Chemotherapy Number at risk 01224364860 Time (months) Induction Chemotherapy Induction Chemoradiation Log-rank P=0.36 5-year Survival (95% CI) 47% (39%-55%) 48% (41%-55%) pN1 0.00 0.25 0.50 0.75 1.00 O v era l l S ur v i v a l ( P r o b a b ili t y ) 813718562414305227 781696534375279195 Number at risk 01224364860 Time (months) Induction Chemotherapy Induction Chemoradiation Log-rank P=0.81 45% (42%-49%) 46% (42%-50%) pN2 5-year Survival (95% CI) Induction Chemotherapy Induction Chemoradiation P atients with stage IIIA-N2 non-small cell lung cancer (NSCLC) who have persistent N1 or N2 disease after induction chemotherapy or induction chemoradiation therapy may still be good candidates for surgery. A national retrospective study of patients with stage IIIA-N2 NSCLC who underwent lobectomy after induction therapy found similar outcomes for those with persistent N1 and N2 disease. Patients with persistent N1 disease had 5-year overall survival of 48% vs. 46% for patients with persistent N2 disease (log-rank P = 0.49), reported Jorind Beqari, MD, University of Massachusetts Medical School-Baystate, Springfield, MA. “Persistent N1 or N2 disease after induction chemotherapy or induction chemoradiation for stage IIIA-NC non-small cell lung cancer should not be an absolute contraindication to surgical intervention” he said. Dr. Beqari presented results during OA20: Exploring Treatment Modalities and Tools in Locally Advanced NSCLC on September 13. This may be the largest study of the role of surgery for patients with stage IIIA-N2 NSCLC with persistent nodal disease based on national data, he noted. Earlier studies were based on single institution data. Researchers queried the National Cancer Data Base (NCDB) for patients with clinical T1-3 N2 M0 NSCLC who underwent lobectomy after induction chemotherapy or chemoradiation therapy who had persistent pantologic N1 or N2 disease from 2004 to 2017. They found 511 patients with N1 disease—231 who had received induction chemotherapy and 280 who had induction chemoradiation—and 1,710 patients with N2 disease—854 who had induction chemotherapy and 865 who had induction chemoradiation. Patients were similar across the groups, Dr. Beqari said, with an average age of 62 years, they were primarily White (87%) and female (55%), and most (68%) had a Charlson- Deyo comorbid condition score of 0. Perioperative outcomes were good in both groups, he said. Thirty- day readmission rates were 2.9% for patients with N1 vs. 3.1% for patients with N2 (P = 0.83) disease; 30-day mortality was 2.8% and 1.7% (P = 0.12), respectively. Ninety- day mortality was 5.9% and 3.8%, respectively (P = 0.05). As noted, there was no significant difference in 5-year survival between patients with N1 and N2 disease, nor were there significant differences in 5-year survival between those who received induction chemotherapy and induction chemoradiation in either patients with N1 (47% vs. 48%, log-rank P = 0.36) or patients with N2 (45% vs. 46%, log-rank P = 0.81) disease. “The authors highlighted and tried to tease apart the clinical differences between N1 and N2 disease,” said discussant Leah M. Backhus, MD, associate professor of cardiothoracic surgery and co-director, Thoracic Surgery Clinical Research Program, Stanford Comprehensive Cancer Center, Stanford University. “Most previous studies had lumped together N0 and N1 disease versus N2 disease.” PERSISTENT N1, N2 DISEASE AFTER INDUCTION THERAPY NOT A CONTRAINDICATION TO SURGERY ILST SHOWS PLCO M2012 SCREENING MODEL TO BE MOST EFFECTIVE FOR DETECTION OF HIGH-RISK INDIVIDUALS THE PLCO M2012 RISK PREDICTION model selected significantly more individuals diagnosed with lung cancer as compared with the United States Preventive Services Task Force (USPSTF2013) eligibility criteria. The cancer detection rate was 15.8% higher using the PLCO m2012 model than the USPSTF2013 criteria. Martin Tammemägi, PhD, of Brock University, California, presented results of the International Lung Screening Trial (ILST) comparing the two risk models during OA19: Screening and Early Detection: State of the Art on September 13. “The first big major potential improvement [in lung cancer prevention] has been lung cancer screening using low-dose computed tomography (LDCT),” Dr. Tammemägi said. “Screening is most effective in high-risk individuals, but how do you select high-risk individuals?” According to Dr. Tammemägi, there are currently two approaches. The categorical approach uses age/pack-years/quit- years; an example of this is USPSTF2013. The quantified risk approach is predicted by an accurate validated model; an example of this is the PLCO m2012 . In the study, 5,819 individuals were screened using LDCT in Canada, Australia, Hong Kong, and the United Kingdom. The researchers used a PLCO threshold of ≥ 1.7%/6 years because it led to equal numbers being positive by each criteria, Dr. Tammemägi noted. In all, 3,509 participants were positive by both criteria; 126 lung cancers occurred in this group. In those who were USPSTF positive and PLCO m2012 negative, nine lung cancers were detected. In those that were PLCO m2012 ≥ 1.7%/6 years and USPSTF negative, 36 lung cancers were detected. The cancer detection rate was 94.7% for PLCO m2012 of ≥ 1.7%/6 years compared with 78.9% for USPSTF criteria. Of all 171 lung cancers detected, 27 more were detected by PLCO m2012 , for a difference of 15.8% more lung cancers than USPSTF2013 criteria (P < 0.001). Compared with the USPSTF positive participants, PLCO m2012 of ≥ 1.7%/6 years selected participants who were older (63.27 vs. 65.68), had more comorbidities, and had shorter model estimated life expectancy (14.8 vs. 13.9 years). “These statistics favored the task force criteria,” Dr. Tammemägi said. However, the cumulative sum of life-expectancies in those participants who developed lung cancer was significantly greater in the PLCO m2012 - selected participants compared with the USPSTF2013-selected individuals. The difference in cumulative life expectancy was 248 years in favor of PLCO m2012 (P = 0.015). “Cost-effectiveness and model- based analyses should use realistic age and life-expectancy difference between categorial and model-based selection criteria,” Dr. Tammemägi said. “The PLCO model has been retrospectively validated in the NLST study, and the work of Dr. Tammemägi and colleagues over the last decade has shown that it is better at participant screening compared to NLST or USPSTF criteria,” said discussant Annette McWilliams, MBBS, FRACP, MD, FRCPSC, of Fiona Stanley Hospital, University of Western Australia, “[It] better defines those that will benefit from LDCT screening.” Martin Tammemägi, PhD Jorind Beqari, MD4IASLC WORLD CONFERENCE ON LUNG CANCER | #WCLC21 PATIENTS with operable malignant pleural mesothelioma (MPM) had significant variability in access to care in the United States, according to a recent study. Those patients with increased access were more likely to receive surgery. Estelamari Rodriguez, MD, MPH, University of Miami Sylvester Comprehensive Cancer Center, presented results of a study examining socioeconomic disparities among patients with MPM during OA13: Topics of Pleural Mesothelioma on September 12. The study examined data from the National Cancer Database on 2,804 patients with stage I-IIIA MPM who were treated from 2004 to 2017. Of the patients who had surgery for MPM, the majority were men (70%), White (83.1%), stage I-II (86.7%), and had epithelioid mesothelioma (58.9%). Patients with increased access to care (for example, living closer to the facility) were more likely to have surgery. Patients who had surgery were also more likely to get treated at an academic center (57.3%) or a higher-volume facility. Only 1.6% of patients who received surgical treatment lived in rural areas. There was no difference in receipt of surgical treatment by educational attainment. A multivariate analysis that adjusted for tumor characteristics, socioeconomic status, and facility-related variables showed no significant difference in overall survival (OS) by race, neighborhood socioeconomic status, insurance, educational attainment, Comorbidity Index, or facility type and volume. Poor OS was more common with advanced age (adjusted hazard ratio [aHR] = 1.02; 95% CI: 1.02-1.03) and male gender (aHR = 1.43; 95% CI: 1.29- 1.58). Surgical treatment in addition to systemic chemotherapy alone (aHR = 0.61; 95% CI: 0.55-0.67; P < 0.001), surgery plus chemotherapy plus radiotherapy (aHR = 0.728; 95% CI: 0.62- 0.86; P < 0.001), and duration of chemotherapy (aHR = 0.998; 95% CI: 0.997-0.999; P < 0.001) were associated with improved OS. The study also showed that patients in the third quartile of annual income ($50,354- $63,332) had better survival than the highest quartile of income ($63,333 or more), with a 17% reduction of overall mortality risk (HR = 0.83; 95% CI: 0.74-0.92; P = 0.001). There was no effect for the two lowest income quartiles (less than $40,227 and $40,227-$50,353) compared with the highest quartile. “Addressing disparities in access to surgery and multimodality therapy can help improve equity of care for patients with MPM,” Dr. Rodriguez said. Discussing the study, Harvey Pass, MD, NYU Langone Health, said that this is a tough but very important study that mirrors previous work that showed that race did not influence survival in patients with MPM who underwent surgery, but that patients who were Black who had surgery had less aggressive treatment than patients who were White. INCREASED ACCESS TO CARE FOR MPM LINKED TO LIKELIHOOD OF SURGERY Estelamari Rodriguez, MD, MPH AGE DOES NOT APPEAR TO AFFECT BENEFIT OF ICIs FOR STAGE IV NSCLC CHRONOLOGIC AGE DID NOT impact survival benefit from immune checkpoint inhibitors (ICIs) in stage IV non-small cell lung cancer (NSCLC), according to a large real-world database analysis. Shinkichi Takamori, MD, PhD, the National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan, presented results of the analysis during MA15: Real World Factors Affecting Lung Cancer Outcomes on September 13. “Elderly patients with NSCLC are likely to be excluded from clinical trials due to their lower functional capacity; therefore, survival benefits from ICIs in elderly patients remains unclear,” Dr. Takamori said. Dr. Takamori and colleagues queried the National Cancer Database for patients with stage IV NSCLC aged 75 or older and those younger than 75 between 2014 and 2015. Overall survival (OS) of more than 86,000 patients who received ICIs and those who did not receive ICIs were com- pared by chronologic age. A univariate analysis in patients younger than 75 years showed that patients treated with ICIs had significantly better OS (hazard ratio [HR] = 0.67; 95% CI: 0.65-0.68), with a 6.7 months improvement in OS compared with no ICI. Among patients aged 75 or older, ICI treatment was also associated with improved survival (HR = 0.61; 95% CI: 0.58-0.64), with a 6.3-month survival benefit compared with no ICI. Survival benefit from ICIs was not affected by age, Dr. Takamori said. Multivariate analysis confirmed the survival benefit from ICIs for patients younger than 75 (HR = 1.47) and those 75 or older (HR = 1.63). These results are in line with those from a pooled analysis of patients aged 75 and older and patients aged younger than 75 from the KEYNOTE-010/042/024 trials that showed that chronologic age did not impact survival benefit from ICIs, Dr. Takamori noted. “These findings should be validated in future prospective studies,” Dr. Takamori added. In his discussion of the study results, Andrew Robinson, MD, FRCPC, Queen’s University, Canada, addressed concerns about the possibility of immortal time bias. When looking at the results, he said, one must consider what happens before “time zero.” Time zero for the real-world patients was time of diagnosis as compared with time of random assignment for patients in clinical trials. In this type of situation, survival time from a diagnosis- time zero to receipt of second- line ICI can be falsely attributed to the intervention. “The similarity in survival differences in these groups does not mean a similar benefit of therapy,” Dr. Robinson said. Shinkichi Takamori, MD, PhD The Official Newspaper of the IASLC 2021 World Conference on Lung Cancer WCLC 2021 Meeting News is published by the International Association for the Study of Lung Cancer (IASLC). IASLC Headquarters is located at 999 17th Street, Suite 200, Denver, Colorado 80202-2725, USA Disclaimer: The ideas and opinions expressed in WCLC 2021 Meeting News do not necessarily reflect those of the IASLC. The mention of any product, service or therapy in this publication should not be construed as an endorsement, and the Association accepts no responsibility for any injury or damage to person or persons arising from or related to any use of material contained in this publication or to any errors or omissions. TriStar Event Media, LLC 7285 West 132nd Street, Suite 300, Overland Park, Kansas 66213 | www.tristareventmedia.com WCLC MEETING NEWS #WCLC21 Cox Regression On a multivariable analysis , there was no Diff in OS by Race, Neighborhood SES, Insurance, Education, Comorbidity Index, Facility Type & Volume Predictors of Poor Overall Survival • Advanced Age (HRadj:1.02, CI:1.02-1.03) Male Gender (HRadj: 1.43,CI:1.29-1.58) Predictors of Improved Overall Survival •Surgery + Chemotherapy (HRadj: 0.606 CI: 0.55-0.67) •Surgery + Chemo +RT (HRadj: 0.73, CI: 0.62-0.86) •Prolonged Chemotherapy (HRadj: 0.998 CI: 0.997-0.999), all P<.001. Do you have a plan to test for RET ? Ensure your testing methods include RET Consider NGS for your patients Retevmo ® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Other product/company names mentioned herein are the trademarks of their respective owners. PP-SE-US-0786 08/2021 © Lilly USA, LLC 2021. All rights reserved. NGS=next-generation sequencing; RET=rearranged during transfection. VISIT RETEVMO.COM/TEST TO LEARN MORE ABOUT TESTING METHODS FOR THIS ACTIONABLE BIOMARKER6IASLC WORLD CONFERENCE ON LUNG CANCER | #WCLC21 IASLC.org/IASLC-News IASLC Lung Cancer News › The ILCN, the IASLC’s official newspaper, has transitioned to an all-digital platform on IASLC.org. › More timely and relevant lung cancer news. More nuanced expert perspectives about clinical care. › More global and multidisciplinary content › Easily discoverable and there when you need it. COVID-19 INCREASES PHYSICAL, MENTAL DIFFICULTIES FOR SOME PATIENTS WITH LUNG CANCER A ccording to a single- institution cohort study, the COVID-19 pandemic has led to treatment modifications for patients with lung cancer in Mexico, including treatment delays and interruptions that led to increased morbidity and mortality with worsened cancer- related outcomes. The combination of fear of potential infection with infectious disease control measures restricting interpersonal and social contact can contribute to increased social isolation, which can boost mental health distress and affect treatment. “Our results underline the relevance of integrating mental health evaluation into the care of patients with thoracic malignancies,” said Oscar Arrieta, MD, MSc, head of thoracic oncology and laboratory of personalized medicine at Instituto Nacional de Cancerologia, Mexico City, Mexico. “We must identify emotional disorders that may be contributing to heightened social isolation and treatment interruptions. Patients who suffered treatment delays or interruptions during the pandemic had worse cancer-related outcomes.” Multiple studies suggest patients with thoracic cancers are a highly vulnerable population with increased risks for morbidity and mortality during the COVID-19 pandemic, Dr. Arietta noted. This study was conducted to assess the impact of COVID-19 on patients, their treatments, outcomes, and mental health statuses. He presented the results during OA17: Multidisciplinary Care of Thoracic Oncology Patients During COVID-19 Pandemic on September 12. The survey followed 548 consecutive patients with thoracic neoplasm between March 1 and December 31, 2020, to determine the impact of psychological disorders related to COVID-19 on patient care and outcomes. Suspension of therapy soared from 8.7% before the pandemic to 37.4%. The most common reasons for suspending treatment were to avoid COVID-19 exposure (35.1%) and suspected (19.1%) or confirmed (10.7%) SARS-CoV-2 infection. “Multivariate analysis shows that patients with any treatment modification remained at higher risk for death, with a hazard [ratio] of 2.3 compared with those without treatment modification,” Dr. Arietta reported. “Treatment modifications were also independently associated with higher risk for progression of 4.2.” Mental health evaluation using the DASS-21 questionnaire showed that 18.2% of patients had symptoms of depression, 30.8% anxiety, and 18.2% stress. Women were more strongly affected than men, with mean DASS-21 scores of 11.41 and 9.08, respectively. In this population, depression, stress, and anxiety all increased the risk of treatment delays, with hazard ratios of 4.5, 3.18, and 1.8, respectively. “Social and clinical interaction was affected by COVID,” said discussant Michelle M. Turner, MS, CRNP, Thoracic Oncology Nurse Practitioner Manager at the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, MD. “Patients were isolated. Their friends, families, providers could no longer touch, hug, or visit. COVID has isolated them, and depression increased. COVID has highlighted the continued need for mental health support for our patients, families, medical providers, and first responders.” Oscar Arrieta, MD, MScPOST EDITION | WORLDWIDE VIRTUAL EVENT7 IN CASE YOU MISSED IT... THE COVID-19 PANDEMIC HAS HAD a dramatic impact on lung cancer trials around the world. Initial data from an IASLC survey of trials in 45 countries found that lung cancer trial enrollment in 2020 declined by 43% compared to the same months in 2019. “The COVID-19 pandemic created many challenges, causing reductions in lung cancer clinical trial enrollment,” said Matthew Smeltzer, PhD, associate professor of epidemiology, biostatistics, and environmental health at the University of Memphis School of Public Health, USA. “Mitigation strategies were employed, and although the pandemic worsened later in 2020, enrollment began to improve as a result of those strategies.” Dr. Smeltzer presented the results of an IASLC Global Clinical Trial Survey during the Presidential Symposium on September 9. The survey queried investigators via email and collected enrollment data for lung cancer trials worldwide for 2019, pre-COVID, and during the pandemic, 2020-2021. Sites were identified using a multi- stage referral process based on recommendations of the Executive Committee and Steering Committee, Dr. Smeltzer said. Trial enrollment fell by 43% in 2020 compared with 2019. Trial enrollment was down in January, February, and March 2020 compared with 2019 enrollment numbers, with the largest decreases reported between April and August. Trial enrollment remained below 2019 levels through December 2020, but the pandemic’s impact on trial enrollment was significantly less between October and December. The most frequent challenges reported by sites included fewer eligible patients, reported by 67% of sites, protocol compliance (61%), suspension of trials (60%), research staff availability (48%), and institutional closures (39%). Patient challenges included willingness to visit trial sites (63%), ability to travel (60%), access to the trial site (52%), exposure-related quarantine (40%), and COVID-19 infection (26%). Fear of COVID-19 infection topped the list of patient concerns (83%), followed by travel restrictions (47%), securing transportation (38%), and laboratory/ radiology access (14%). COVID-19 SLOWS LUNG CANCER TRIALS GLOBALLY Matthew Smeltzer, PhD LUNG CANCER IS A GLOBAL problem, but the burden does not weigh equally. There are stark disparities in diagnosis, treatment, and outcomes. One telling measure is the proportion of non-small cell lung cancer (NSCLC) patients diagnosed with stage IV disease. Stage at diagnosis is a useful surrogate for health care resources, noted Alex A. Adjei, MD, PhD, professor of oncology and pharmacology at the Mayo Clinic, Rochester, MN. “Some countries—the United States and United Kingdom—have less than 50% of NSCLC cases diagnosed at stage IV,” Dr. Adjei reported during Opening Plenary: Access & Disparities on September 8.“Whereas a number of areas in Asia and Africa have 70% or more of the NSCLC cases diagnosed at stage IV.In Ethiopia, with 85% of NSCLC diagnosed at stage IV, typically patients are empirically treated with antituberculosis agents before a lung cancer workup is even begun.” The disparities of lung cancer burden are not obvious at first glance, said Dr. Adjei, who is also editor-in-chief of the Journal of Thoracic Oncology and JTO Clinical and Research Reports. Lung cancer is the second-most common cancer worldwide after breast cancer and the leading cause of cancer mortality. And, not surprisingly, lung cancer incidence is similar to global population distribution. Treatment options vary widely. “In the rest of the world, there’s a problem of accessibility and availability,” he said. “In South Africa, for example, there is no availability of immunotherapy or targeted agents in the public sector. Even in the private sector, which is more affluent, there is limited availability. This is the situation in most parts of Africa, South America, Asia, and Eastern Europe.” The IASLC can boost partnerships with other societies, champion biosimilars, and work with pharmaceutical companies to combat high prices, Dr. Adjei said. It also must pay greater attention to underrepresented parts of the world in projects, activities, and initiatives, and increase membership from currently underrepresented regions. The highest lung cancer death rates in the United States are in Kentucky, Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, said Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at the Baptist Memorial Healthcare Corporation and director of the Multidisciplinary Thoracic Oncology Program and the Thoracic Oncology Research Group at the Baptist Cancer Center, Memphis, USA. “There is a mismatch between the places where lung cancer kills and the places we have invested in low-dose CT screening in the United States,” said Dr. Osarogiagbon, who also is a member of the IASLC Staging and Prognostic Factors Committee. “And when you look at screening eligibility criteria, there is a striking disparity by race and sex. Our policy-level screening criteria actually drive racial disparities in access to lung cancer screening.” GLOBAL DISPARITIES IN LUNG CANCER DIAGNOSIS, TREATMENT, OUTCOMES Alex A. Adjei, MD, PhD AIR POLLUTION A FACTOR IN FIGHT AGAINST LUNG CANCER D uring the Presidential Symposium at WCLC 2021, Christine D. Berg, MD, former director of National Lung Screening Trial, called upon the health care community and lung cancer professionals to act against air pollution. “Air pollution contributes to 14% of lung cancer deaths worldwide,” Dr. Berg said during her presentation. “At this level that makes it the second leading cause of lung cancer in the world.” Dr. Berg cited a report published in 2020 (Turner MC, Andersen ZJ, Baccarelli A, et al) estimating that there were 1.8 million deaths in 2018 from lung cancer worldwide. In 2017, it was estimated that 265,267 lung cancer deaths were attributable to air pollution. In the United States, these numbers are slightly better, with air pollution estimated to contribute to about 4.7% of lung cancer deaths. The International Association for Research on Lung Cancer has identified indoor emissions from household combustion of coal, diesel engine exhaust, and outdoor air pollution, particularly particulate matter, as hazard assessment group 1 carcinogens—the same category as cigarette smoking. The Global Burden of Disease Study (Cohen AJ, Brauer M, Burnett R, et al), published in 2017, estimated the deaths from lung cancer in countries across the globe and included an estimation of particulate matter exposure. Dr. Berg noted that this was the first year that the IASLC had issued a statement in support of International Clean Air Day, which was September 7, 2021. She encouraged other lung cancer professionals to get involved, as well. Dr. Berg and Joan H. Schiller, MD, of the University of Virginia and the 2020 recipient of the IASLC Paul A. Bunn, Jr. Scientific Award, are forming an interest group on air pollution and lung cancer to look at additional research and how the health care community can help ameliorate the problem. Christine D. Berg, MD Read the complete versions of these articles and more coverage in the WCLC Meeting News digital editions, available at www.iaslc.org/WCLC21-News.Reference: COSELA (trilaciclib). Prescribing Information. G1 Therapeutics, Inc; 02/2021. G1 Therapeutics™ and the G1 Therapeutics logo, COSELA™ and the COSELA logo are trademarks of G1 Therapeutics, Inc. ©2021 G1 Therapeutics, Inc. All rights reserved. US-2100258 07/2021 SPARE THE MARROW. COSELA HELPS PROTECT AGAINST MYELOSUPPRESSION, PROACTIVELY HELP PROTECT AGAINST MULTIPLE MYELOSUPPRESSIVE CONSEQUENCES WITH THE FIRST AND ONLY MYELOPROTECTION THERAPY The Pivotal Study (Study 1) compared an etoposide/carboplatin + atezolizumab (E/P/A) regimen with COSELA vs without COSELA* To decrease the incidence of chemotherapy-induced myelosuppressionin patients when administered prior to a platinum/ etoposide-containing regimen or topotecan-containing regimen FOR EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC) COSELA™ (trilaciclib) helps protect hematopoietic stem and progenitor cells (HSPCs), the source of blood cell lineages INDICATION COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). * COSELA was evaluated in 3 randomized, double-blind, placebo-controlled clinical studies. The Pivotal Study (Study 1) evaluated COSELA or placebo administered prior to treatment with E/P/A in 107 patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. In this study, COSELA significantly reduced the primary endpoints of incidence (adjusted relative risk [aRR] 0.038 [95% CI, 0.008, 0.195], P<0.0001) and duration in Cycle 1 (mean difference -3.6 [95% CI, -4.9, -2.3], P<0.0001) of severe neutropenia and significantly decreased the rate of all-cause chemotherapy dose reductions (aRR 0.242 [95% CI, 0.079, 0.742]). The incidence of Grade 3/4 anemia was 19% and 28% (aRR 0.663 [95% CI, 0.336, 1.310]) and RBC transfusions on/after 5 weeks were 13% and 21% (aRR 0.642 [95% CI, 0.294, 1.404]) with and without COSELA, respectively. VISIT COSELA.COM FOR MORE DETAILSTo report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. This information is not comprehensive. Please see the Brief Summary of Prescribing Information on the adjacent page. SPEAR THE TUMOR. WHILE CHEMOTHERAPY TARGETS CANCER CELLS SELECT IMPORTANT SAFETY INFORMATION CONTRAINDICATION • COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. WARNINGS AND PRECAUTIONS Injection-Site Reactions, Including Phlebitis and Thrombophlebitis • COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients. Acute Drug Hypersensitivity Reactions • COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA. Interstitial Lung Disease/Pneumonitis • Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin- dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/ pneumonitis, and severe (Grade 3) or life-threatening (Grade 4)ILD/pneumonitis, permanently discontinue COSELA. Embryo-Fetal Toxicity • Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose. ADVERSE REACTIONS • The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. 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