A n embedded onco- palliative care clinic increased early referrals to palliative care and improves patient access to outpatient palliative care concurrent to standard oncology treatment, according to the results of a study presented at WCLC 2021. “We feel embedded outpatient palliative care is a feasible care delivery model that can increase ambulatory palliative referrals for patients with a thoracic malignancy,” said study presenter Julia L. Agne, MD, The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, during OA05: Palliative Care Service Models . According to Dr. Agne, the past decade has shown tremendous growth in outpatient palliative care resources especially at National Cancer Institute-designated cancer centers. This growth has resulted in several new clinical models for outpatient palliative care. At Dr. Agne’s institution, there are three models for palliative care: • The freestanding model serves all patients with cancer regardless of diagnosis. It is freestanding, remote, and requires patients to have a separate palliative care clinic, which frequently cannot be coordinated on the same day as other services, she said. CONQUERING THORACIC CANCERS WORLDWIDE SUNDAY, SEPTEMBER 12 INSIDE: PAGE 4 Cessation efforts at screening PAGE 7 MPM and COVID-19 mortality PAGE 11 Bi-specific agents in clinical trials PAGE 3 Size T descriptor classification PAGE 12 Non-recommended EGFR+ treatment CHEMOTHERAPY PLUS IMMUNE CHECKPOINT INHIBITION EFFECTIVE IN NSCLC WITH UNTREATED BRAIN METASTASES BRAIN METASTASES ARE THE most frequent complication of non-small cell lung cancer (NSCLC) and can have a major impact on both cancer-related and neurologic outcomes, neurocognitive function, quality of life, and overall prognosis. Yet for patients with NSCLC, untreated brain metastases have largely been excluded from first-line trials of chemotherapy plus immune checkpoint inhibition. A single-arm study of combination therapy in this distinct population yielded promising results. “The safety profile and efficacy of atezolizumab combined with carboplatin and pemetrexed is favorable in [patients with] NSCLC with untreated brain metastases, including those who are receiving corticosteroids,” said Ernest Nadal, MD, PhD, head of thoracic tumors, Catalan Institute of Oncology, Spain. “This combination can result in clinical benefit in terms of overall survival in this population, with 32% of patients alive at two years.” Dr. Nadal reported the results of ATEZO-BRAIN during OA09: Expanding Immunotherapy Options for Non-small Cell Lung Cancers on Thursday. The trial enrolled 40 patients with stage IV non-squamous NSCLC and untreated brain metastases who were treatment naïve for immune checkpoint Julia L. Agne, MD ... see COMBINATION on page 15 EMBEDDED PALLIATIVE CARE MODELS INCREASED REFERRAL RATES IN THORACIC MALIGNANCIES ... see PALLIATIVE on page 14 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. Ernest Nadal, MD, PhD Primary Endpoint: Systemic and Intracranial PFS Median follow-up 17.3 months Systemic PFS by RECIST v1.1 Intracranial PFS by RANO-BM Survival Probability Survival Probability Time (Months) Time (Months) 0 3 6 9 12 15 18 21 24 0 3 6 9 12 15 18 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0 Median PFS = 8.9 months (95% CI 6.7–13.8) 18 months PFS rate = 24.9% Median icPFS = 6.9 months (95% CI 4.7–12.1) 18 months icPFS rate = 10.4% 37 28 19 14 11 9 2 1 1 37 28 23 16 13 10 2LOCATION 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?SUNDAY, SEPTEMBER 12, 2021 | WORLDWIDE VIRTUAL EVENT 3 B etter recruitment of institutions, countries, and continents will ensure that the dataset being included in the IASLC’s Staging and Prognostic Factors Committee (SPFC) global molecular database reflects the global epidemiology of lung cancer, according to a presentation by Raymond U. Osarogiagbon, MBBS, FACP, Baptist Cancer Center, Memphis, Tenn., during OA06: Prognosis and Staging Oral Abstract session during WCLC 2021. “The IASLC took on responsibility for providing evidence to guide the evolution of the TNM Staging System for thoracic oncology with the 7th edition,” Dr. Osarogiagbon said. “For the first time, with the 9th edition, the staging and prognostic factors committee engaged in constructing a global molecular database for thoracic malignancies.” This database is necessary because biomarker-directed treatment and prognostication are rapidly changing lung cancer care worldwide. The present reality is that anatomy-based prognostication is insufficient, he added. The database is accumulating molecular biomarker data to complement TNM-based prognostication. Dr. Osarogiagbon and colleagues recently evaluated the first effort of the SPFC global molecular database by analyzing lung cancer cases from consenting institutions who submitted data from patients diagnosed from 2010 to 2019 and staged by the 8th edition of the TNM Staging System. They primarily focused on cases from electronic data capture (EDC). Of the 64,434 cases currently in the SPFC NSCLC database, 10% were EDC cases, of which about one-third (31%) had biomarker data. All cases were submitted from Asia/Australia (79.4%), North America (7.8%), and Europe (7.8%). Dr. Osarogiagbon said the program could use much more support from North American institutions which unfortunately form the minority of institutions submitting cases, “Despite the fact that biomarker testing is probably more frequent in the United States than in other countries”. Biomarker data was from only 14 countries, including China (28%), Canada (25%), Spain (15%), Australia (10%), and India (5%). More of the cases with biomarker data are adenocarcinoma (76%). In addition, most cases with biomarker data are stage 0-IB (27%) or IIA-IIB (30%). “Most of the biomarker information are single-gene tests,” Dr. Osarogiagbon said. The most common was EGFR testing, which is present in about 70% of all cases. Of those tested, 23% had EGFR mutations. PD-L1 testing was done in 59% of cases. Dr. Osarogiagbon said the data reflect the huge potential for constructing a global database, which will create insights into patterns and outcomes of lung cancer care, but there is still much work to be done. Study discussant Jorge Alatorre- Alexander, MD, Instituto Nacional Enfermedades Respiratorias, Mexico, said he agreed with need for a global effort to get more information about biomarkers in more populations, with this early and interesting data reflecting the true heterogeneity of this patient population. GLOBAL MOLECULAR DATABASE PROVIDES INSIGHTS INTO LUNG CANCER WORLDWIDE Raymond U. Osarogiagbon, MBBS, FACP Submissions With v Without Biomarker Data Variable No Biomarker Data N= 4543 Biomarker Data, N – 2068 P Continent (%) Asia/Australia North America Europe South/Central America Africa/Middle East 1373 (30) 1645 (36) 1239 (27) 266 (5) 20 (0) 1014 (49) 586 (28) 444 (21) 23 (1) 1 (0) <0.001 Histology (%) Adenocarcinoma Squamous Others 2889 (64) 1352 (30) 207 (5) 1573 (76) 355 (17) 129 (6) <0.001 Aggregate clinical stage (%) 0 — IB IIA — IIIB IIIC — IVB 2642 (61) 1264 (29) 420 (9) 549 (27) 623 (30) 844 (41) <0.001 Treatment (%) Surgery Chemotherapy Immunotherapy Radiation Therapy 3626 (82) 1268 (30) 73 (2) 642 (15) 945 (46) 983 (52) 291 (15) 424 (22) <0.001 NO LEPIDIC COMPONENT NEEDED FOR PREDICTING OUTCOMES USING T DESCRIPTOR CLASSIFICATION T he presence of a lepidic component was not an independent prognostic factor in early-stage lung non-mucinous adenocarcinomas, supporting the current TNM recommendation to use invasive size for the size T descriptor rather than a different approach. Yan Li, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, presented data from a study investigating whether the presence or proportion of the lepidic component was associated with patient outcomes within the same pathologic stage according to invasive size. According to Dr. Li, the 8th Edition of the TNM Classification of Malignant Tumors excluded a lepidic component and had primary lung nonmucinous adenocarcinomas fall into the same pathologic stage as pure invasive tumors with the same invasive size. However, the favorable survival seen with part lepidic tumors raised the question of whether these tumors should be staged differently, she said during OA06: Prognosis and Staging. Study discussant Jorge Alatorre- Alexander, MD, Instituto Nacionalde Enfermedades Respiratorias, Mexico, agreed that there is still some controversy in this field, with some studies suggesting that invasive rather than total size probably does matter and others saying it may not matter. The study included 1,704 patients with primary pT1a-2bN0M0 lung adenocarcinoma who underwent tumor resection for primary lung nonmucinous adenocarcinoma from 2000 to 2014. They stratified patients by 0%, 25% or less, 50% or less, and greater than 50% lepidic component. There was a statistically significant improvement in all outcomes observed in patients that had any lepidic component. With all pathologic T stages combined and stratified by proportion of lepidic component, differences in outcomes were most evident when comparing the 25% or less and greater than 25% levels. However, when the researchers compared patients by stage there was no statistically significant difference in disease-free survival consistently observed across all stage categories for any lepidic component. The results were the same for lung cancer-specific incidence of death or cumulative incidence of recurrence. Based on these results, Dr. Li said that “the current pathological T classification based on invasive size is adequate for predicting outcomes, without revision according to the presence or absence of lepidic component.” Yan Li, MD, PhD4 IASLC WORLD CONFERENCE ON LUNG CANCER | #WCLC21 I n 2020, the IASLC issued a declaration emphasizing the importance of tobacco cessation after cancer diagnosis, calling a cancer diagnosis a “teachable moment” that allows health care professionals an opportunity to discuss nicotine addiction. At WCLC 2021, another teachable moment for smoking cessation was discussed during ES01: Proactive Tobacco and Cancer Control Education Session on Friday. Emily Stone, MBBS, PhD, FRACP, St Vincent’s Hospital Sydney, Kinghorn Cancer Centre, University of NSW, Australia, presented information on the importance of discussing smoking cessation during low-dose CT (LDCT) lung cancer screening. Some of the best data to highlight smoking cessation comes from a single-center study published in 2015 that looked at about 300 patients with new lung cancer diagnoses who were referred for smoking cessation. At the first follow-up contact, 28.7% of patients had quit smoking, and 41.8% had quit by the second contact. The study showed a significant increase in survival associated with quitting compared with continued tobacco use. Dr. Stone, who is a member of the IASLC Tobacco Control and Smoking Cessation Committee, called these results “remarkable and gratifying.” Lung cancer survivors are also candidates for smoking cessation efforts, Dr. Stone said. A recent study looked at risk factors for the development of second primary lung cancers among more than 7,000 lung cancer survivors and identified tobacco smoking—both pack-years and intensity—as a significant risk factor. However, perhaps more attention is needed to addressing smoking cessation at the time of lung cancer screening, Dr. Stone said. Cessation and screening studies In the National Lung Screening Trial in the United States, researchers attempted to quantify the effects of smoking history and abstinence on mortality in high-risk individuals undergoing screening. The study showed that individuals with a smoking history who had been abstinent for 7 years had a 20% reduction in mortality, but the maximum benefit—about 40% reduction in mortality—occurred in those who had an abstinence of 15 years combined with LDCT screening. These results highlight the importance of smoking cessation efforts in screening programs. Screening is likely a teachable moment and could lead to cessation, Dr. Stone said, but the topic is complex. Research into the combination of smoking cessation and screening are ongoing. The SCALE collaboration is a group of studies in the United States designed to gain knowledge from clinical trials about effective strategies for smoking cessation for people undergoing lung cancer screening. The studies will have a wide variety of interventions, including counseling, interviewing, and digital advice. An analysis of reasons to avoid smoking cessation has been done for at least six of these SCALE studies, Dr. Stone said. Among the most common reasons for people not participating in smoking cessation programs were that they are “not interested” or are “passive,” meaning they are eligible and approached but never reached out for the trial. “These first two groups offer the most potential for intervention— not-interested or passive. I think its studies like the SCALE studies that will look into the fine details of why these people may not be motivated or simply hard to reach,” Dr. Stone said. Another recent study looked at predictors of attribution from smoking cessation trials in lung cancer screening. The study found that among patients offered smoking cessation after lung cancer screening higher education levels were associated with less attrition and higher intensity smoking jeopardized participation in cessation. Dr. Stone also highlighted several smoking cessation studies taking place in Europe. For example, the Yorkshire Enhanced Stop Smoking (YESS) study protocol, published last year, will use incidental findings as part of a smoking cessation intervention delivered alongside lung cancer screening. As part of the intervention, participants will receive a personalized booklet with LDCT scan images. Participants with identified emphysema or coronary artery calcification will get images of these conditions along with text to provide context and explanations. “It will be interesting to see what happens with these results in terms of smoking cessation,” Dr. Stone said. Results of the ITALUNG study were also published last year. This study compared smoking cessation rates in people invited to a free smoking cessation program who did or did not also receive LDCT. There were consistently higher quit rates in participants with CT screening than in those without, Dr. Stone said. The NELSON study, which identified helpful factors associated with prolonged smoking abstinence including higher education, and the UK Lung Cancer Screening Trial that showed that CT screening increased quit rates at 2 weeks after scan results and up to 2 years after trial recruitment. Guidelines for smoking cessation in LDCT screening do exist, Dr. Stone said, but there are not many. In 2016, Fucito and colleagues with the Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco published recommendations for pairing smoking cessation services with lung cancer screening. These recommendations included encouraging patients to quit at all visits, active assistance for referral to cessation programs, and providing behavioral strategies if treatment medication is declined. The guideline also highlighted the need for research into optimal strategies and the barriers and negative effects of screening on smoking cessation. Stone closed her discussion with a quote from the American Cancer Society Guidelines, “Current smokers should be informed of their continuing risk of lung cancer and referred to smoking cessation programs. Screening should not be viewed as an alternative to smoking cessation.” Other tobacco control efforts Also during the session, Charis Girvalaki, PhD, European Cancer Patient Coalition (ECPC), Belgium, discussed the influence of lung cancer care providers in tobacco control and policy advocacy. The ECPC works to influence the EU legal framework and the European and national political agenda. Working through a coalition has certain advantages, she said, including accessing, sharing, and disseminating information, pooling resources, and garnering decision makers’ support. “Cancer diagnosis, especially with lung cancer due to direct link to smoking, may provide a useful teachable moment for quitting smoking, but this chance is frequently undervalued by the health care system,” Dr. Girvalaki said. “EU legislative measures to bring forth tobacco control and smoking cessation, and reinforcement of advocacy and policy actions are needed at the European level. ... We at ECPC are determined to contribute to this cause.” Joelle Fathi, DNP, ARNP, CTTS, University of Washington, USA, also supported the use of advocacy for global tobacco control in her presentation, which discussed how to set up clinical tobacco cessation efforts for success. She discussed that many who chose to smoke are open to cessation, but often are not getting what they need to quit. “Tobacco cessation is never easy, and the journey is never over,” said Ms. Fathi, who is also a member of the IASLC Tobacco Control and Smoking Cessation Committee. “We must build health systems that prioritize tobacco work and address tobacco use with every touch point, with recovery as the end goal.” Ms. Fathi said there is a need to engage in key partnerships and advocate for policies at all levels to eradicate tobacco and its detrimental health effects. EMPHASIZING SMOKING CESSATION AT TIME OF SCREENING AN ESSENTIAL PART OF TOBACCO CONTROL Emily Stone, MBBS, PhD, FRACPDo 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 BIOMARKERRESEARCHERS HAVE DEVELOPED a novel blood-based diagnostic model based on the expression of four microRNAs (miRNAs) that had high sensitivity and specificity, even in detecting early-stage lung cancers. Andrew Zhang, Del Norte High School, San Diego, Calif., presented a study of this new model during MA07: Liquid Biopsy Applications for Immuno- oncology, Targeted Therapies, and Early Stage NSCLC on Thursday, September 9, at WCLC 2021. Early lung cancer detection is essential for decreasing mortality. Low-dose CT is the current standard technology for screening but has several limitations. A readily available diagnostic test, like a routine blood test, with high accuracy is needed, Mr. Zhang said. Mr. Zhang and colleagues performed a study based on a large miRNA dataset, made publicly available through a Japanese nationwide research project designed to characterize 2,588 serum miRNA profiles across 13 cancer types. In the original study, researchers developed a diagnostic model with two miRNAs, which had a sensitivity of 95% and specificity of 99%. However, Mr. Zhang noted that even a small improvement in performance could have a substantial impact in reduced false positives and negatives. Therefore, the researchers used the original discovery and validation data sets from the Japanese study to develop a four-miRNA diagnostic model using bioinformatics analysis. Next, they validated this model in the validation set, which included 1,358 patients with lung cancer and 1,970 controls. The new four-miRNA model was superior to the original model with an AUC ROC of 0.999 vs 0.996 in the two-miRNA model. Although both models had 99% specificity, the new four-miRNA model also achieved 99% sensitivity, Mr. Zhang said. “The new model also showed superior performance in all clinically relevant patient subgroups, especially [for those with] stage I cancers,” Zhang said. “This suggests that the new four miRNA model might have the potential to detect lung cancer at early stages with high accuracy before patients have any symptoms.” Finally, Mr. Zhang and colleagues looked at paired serum samples from 180 patients pre- and post-surgical resection. The diagnostic index was dramatically decreased back to normal levels after tumor resection. “This demonstrates that the four miRNAs were likely tumor-derived and that the test could be used to detect for tumor recurrence in the future,” he said. BMI, EPSILON SCORE PREDICTED NSCLC RESPONSE TO IMMUNE CHECKPOINT INHIBITION B oth body mass index (BMI) and EPSILoN score were predictive markers of response to frontline immune checkpoint inhibition (ICI) with or without chemotherapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC), according to a WCLC 2021 poster presenting results of a study. These were predictive regardless of PD-L1 expression, according to Raena D. Rhone, BSEd, PharmD, of Memorial Cancer Institute and Florida A&M University, USA who presented the results in P44: Clinical Predictive Markers of Response to Immunotherapy in Advanced Non- Small Cell Lung Cancer (NSCLC). Studies have shown that overweight and obesity are associated with improved survival and delayed progression in patients treated with ICIs. In addition, the EPSILoN score is a known predictive marker of response to ICIs, Dr. Rhone said. EPSILoN is comprised of five clinical variables— smoking, ECOG performance status, liver metastases, lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio. In this study, Dr. Rhone and colleagues examined if these two factors could predict response to frontline ICI with or without chemotherapy for advanced NSCLC. They also assessed these parameters among different race and ethnic groups. The study included 62 patients; 16% of patients identified as Black and 29% identified as Hispanic. More than one-half of patients had a BMI of 18.5 to 25 kg/m2 (58%); 26% were overweight (BMI 25 to 29), and 14% were obese (BMI of 30 or greater). Dr. Rhone noted that due to lack of routine LDH testing, a modified EPSILoN score was used. Patients with an overweight or obese BMI had significantly longer median progression-free survival compared with normal weight patients (8.9 vs. 5.53 months; HR = 0.54; P = 0.04). Additionally, patients considered overweight or obese with PD-L1 expression of 50% or more had significantly longer progression-free survival than normal-weight patients with PD-L1 expression of 50% or more (not reached vs. 6.73 months; HR = 0.23; P = 0.03). A modified EPSILoN score of 1 was associated with significantly longer overall survival than a score of 2-3 (not reached vs. 11.13; HR = 0.32; P = 0.01). The study also revealed that Black non- Hispanic patients started ICI treatment with more advanced disease compared with White non-Hispanic patients. In addition, fewer Black non-Hispanic patients were overweight and obese compared with White non-Hispanic patients (22% vs. 48%), indicating possible poorer response to ICI. P atients with EGFR/ALK+ non- squamous non-small cell lung cancer (NSCLC) have few good treatment options. Median progression free survival (PFS) with tyrosine kinase inhibitors (TKI) ranges from 10 – 19 months for EGFR+ NSCLC and 10-34 months for ALK+ NSCLC. Platinum- based chemotherapy following TKIs has only a modest benefit. Immunotherapy has similarly limited benefits in EGFR/ ALK+ patients, but the combination of chemotherapy plus pembrolizumab is beneficial in NSCLC without EGFR/ALK alterations. It was not clear what effect, if any, the same combination might have in patients with EGFR/ALK+ NSCLC. “We conducted a phase II trial to evaluate this combination of pembrolizumab plus chemotherapy in recurrent EGFR/ALK-positive NSCLC who had been previously treated with the appropriate TKIs,” said Shirish M. Gadgeel, MD, division head for hematology/oncology, Henry Ford Cancer Institute, Detroit, Mich., during OA09: Expanding Immunotherapy Options for Non-small Cell Lung Cancers on Thursday. Patients in the single-arm, multicenter trial received pembrolizumab plus carboplatin/pemetrexed for four cycles followed by maintenance pemetrexed and pembrolizumab for two years. The primary outcome was the RECIST 1.1 defined response rate, with PFS and overall survival (OS) as secondary endpoints. The study enrolled 26 EGFR+ patients and seven ALK+ patients. Planned enrollment was 42 patients, but the trial was closed early due to the COVID-19 pandemic. Median age was 68 for the EGFR+ patients and 66 for ALK+ patients. Both cohorts were primarily female, and most patients has received just one prior treatment. The median PFS was 8.3 months for EGFR+ patients and 2.9 months for ALK+ patients. At 12 months, 29% of EGFR+ patients and 14% of ALK+ remained progression free. Median survival was 22.2 months for EGFR+ patients and 2.9 months for ALK+ patients. At 12 months, 76% of EGFR+ patients and 14% of ALK+ patients were alive. There was no significant difference in either PFS or OS based on PD-L1 status. All sites used the Dako22C3 assay to determine PD-L1 status. Adverse events were as expected, Dr. Gadgeel reported. “These results warrant further investigation of pembrolizumab plus chemotherapy in patients with recurrent EGFR mutation-positive NSCLC,” he said. CHEMOTHERAPY + IMMUNE CHECKPOINT INHIBITION SHOWS PROMISE IN RECURRENT EGFR/ALK+ NSCLC NOVEL DIAGNOSTIC TEST COULD DETECT EARLY LUNG CANCERS Raena D. Rhone, BSEd, PharmD SCIENCE TO WATCH Shirish M. Gadgeel, MD 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 6 SCIENCE TO WATCH METFORMIN MAY IMPROVE OUTCOMES IN PATIENTS WITH LUNG CANCER AND OBESITY Joseph Barbi, PhD 7 RETROSPECTIVE CLINICAL DATA AND animal models suggest that metformin, a common diabetes drug, may improve lung cancer outcomes, but only for patients who are overweight or obese. “Metformin is widely used, generally well tolerated, cheap, and studied quite extensively for its anti-cancer potential,” said Joseph Barbi, PhD, assistant professor of oncology, Roswell Park Comprehensive Cancer Center, University of Buffalo, Buffalo, N.Y. “In retrospective human studies of lung cancer, all of the benefit for taking metformin in terms of increased survival was in the overweight and obese patient population. We took a transcriptome approach to see whether or not gene expression related to immune function was different in patients that were of high and low [body mass index] in [patients with] advanced stage lung cancer.” The answer is yes, Dr. Barbi said during OA12: Understanding and Augmenting Responses to Immunotherapy for Thoracic Malignancies Oral Abstract session on Thursday. Multiple genes are differentially expressed in response to metformin. Many are related to immune function or dysfunction, including checkpoint inhibitor markers PD1, LAG3, and CTLA4. All were elevated in patients who were obese and overweight, but not in those patients with normal weights. Metformin reduces of these mediators of immune suppression in the tumor microenvironment, but only in patients who were obese or overweight. In mouse models, Lewis lung carcinoma tumors grew far larger in obese mice compared to normal-weight mice. When treated with metformin, tumors in the overweight mice quickly shrank, while tumors in matched normal-weight controls showed no change. Mice given Lewis lung carcinoma cells tagged with luciferase showed similar patterns. Obese mice developed a far greater tumor burden from micro metastatic spread compared to normal- weight mice. And when treated with metformin, the obese mice showed significant reduction in tumor burden while normal- weight mice showed no benefit. The finding could have significant impact as obesity becomes more common in patients with lung cancer and the general population. “Metformin is associated with improved survival and favorably immune programming events in both mice and patients,” Dr. Bari said. “Several of the negative events associated with obesity can be reversed by metformin treatment and may be linked to metabolic reprogramming in the tumor microenvironment.” PLEURAL MALIGNANT MESOTHELIOMA LINKED WITH HIGH COVID-19 MORTALITY H ealth care services should pay particular attention to patients with malignant pleural mesothelioma (MPM) who have COVID-19 infection, according to new data out of Spain. Most of these patients required hospitalization, and the mortality rate was high. Previous research has shown that patients with cancer may be at greater risk for SARS-CoV-2 infection. Data from the TERAVOLT registry—an international registry of patients with thoracic cancers and COVID-19— evaluated the effect of SARS-CoV-2 infection on patients with thoracic malignancies, but the registry only included eight patients with MPM. During MA04: Current Status and Future Prospects of Pleural Mesothelioma and Thymoma, Susana Cedres, MD, PhD, of the Vall d’Hebron University Hospital and Institute of Oncology, Spain, presented data on outcomes of 38 patients with MPM who visited her institution between March 2020 and March 2021. Dr. Cedres and colleagues reviewed the medical records of these 38 patients and collected clinical data on demographics, comorbidities, oncological background, and course of COVID-19 illness. She noted that the aim of the study is descriptive in nature. Of the 38 patients, seven patients (18%) were positive for COVID-19 by a positive RT-PCR test. The median age of patients who tested positive for COVID-19 was 62 years (57% male). All cases had epithelioid histology. The most common comorbidities among these patients were hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. At COVID-19 diagnosis, one patient was actively receiving chemotherapy, and one was undergoing thoracic radiotherapy. Four of the seven patients were symptomatic. There was a median of 4 days between onset of symptoms and COVID-19 diagnosis. All of the symptomatic patients had fever and dyspnea. Asymptomatic patients were tested because of known exposure to a patient with confirmed infection. Six of the seven (85%) positive cases required hospitalization, with a median of 12 days of hospitalization (range from 3-28 days). All hospitalized patients required oxygen support: three with a simple mask and three with a non-re-breather mask. The median overall survival (OS) was 17.8 months from cancer diagnosis. Five of the seven patients died; four patients (57%) due to complications from COVID-19 and one patient due to disease progression. This equated to a mortality rate of 57%. The median OS from time of COVID-19 diagnosis was 0.4 months. In her discussion of these results, Francoise Galateau-Sallé, MD, of Cancer Center Leon Berard, France, noted that it is difficult to compare this study with previous research because there is an overall lack of data. Dr. Galateau-Sallé mentioned several strengths of the study out of Spain, including the much- needed addition of data on seven more patients with MPM. However, she also mentioned several weaknesses of the study, including the lack of data on clinical stage of the disease, the line of chemotherapy, and risk factors more specific to MPM. “There is really a need for more inclusion of [patients with] MPM in international registries in the near future,” Dr. Galateau-Sallé said. “We need extensive registration in an international registry to improve clinical characteristics and outcomes in patients with MPM presenting with COVID-19 infection.” RESULTS 5/7 patients died: 4 patients due to COVID-19 and 1 patient due to PD. Median OS was 0.4 m since COVID-19 diagnosis Susana Cedres, MD, PhD Characteristic at COVID dxNumberPercentage Comorbidity Cardiovascular Respiratory Renal 4 1 1 57 14 14 Concomitant treatment Antiplatelet/anticoagulant Antidiabetic Corticosteroids 4 2 1 57 29 14 Clinical Onset Symptomatic Asymptomatic 4 3 57 43 Labratory Lymphopenia High d-dimer High IL-6 6 4 4 85 57 57 Hospitalization Yes No 6 1 85 14 Respiratory Symptoms Bilateral pneumonia Oxygen support 4 6 57 85Reference: 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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