Lung Cancer Clinical Trials Research Articles

Survival analysis of patients with primary breast duct carcinoma and lung adenocarcinoma: a population-based study from SEER

The appeal to enroll patients with primary breast and lung cancer in clinical trials is increasing, but survival of these two primary cancers remains to be elucidated. This study analyzed the prognosis of primary breast duct carcinoma with subsequent lung adenocarcinoma (BCLA) and primary breast duct carcinoma with prior lung adenocarcinoma (LABC). Cohorts of 3,515 patients with BCLA and 654 patients with LABC were identified from the Surveillance, Epidemiology, and End Results database. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer (mTPC1), or mTPC2 groups when the interval times between breast and lung cancer were within 6 months, between 7 and 60 months, or over 60 months, respectively. The propensity score matching program (PSM) was applied to determine the survival of BCLA/LABC relative to single breast/lung cancer. Cox proportional hazard regression model and competing risk modes were performed to identify confounders associated with all-cause and cancer-specific death, respectively. Survival of patients with LABC/BCLA relative to single breast/lung cancer was accessed via median survival time. The survival of patients with BCLA/LABC was generally poor compared with the survival of those with single breast cancer. The PSM-estimated HR in the sTPC group with BCLA and in the mTPC1 and mTPC2 groups with LABC were 0.75 (95% CI 0.62–0.90), 0.52 (95% CI 0.27–0.98), and 0.36 (95% CI 0.20–0.65), respectively, whereas the SHRs were 0.80 (95% CI 0.66–0.97), 0.68 (95% CI 0.34–1.34), and 0.46 (95% CI 0.27–0.80), respectively, compared with those in the single lung cancer group. By contrast, the survival rates of the remaining patients did not differ. The median survival times since secondary malignancy were 42, 23, and 20 months in the sTPC, mTPC1, and mTPC2 groups with BCLA, respectively, and 18, 60, and 180 months in those with LABC, respectively. For patients with BCLA, the adjusted Cox regression suggested incidences of all-cause deaths in mTPC1group were statically higher than those in sTPC group, whereas the incidences of all-cause and cancer-specific death in the mTPC1 and mTPC2 groups were statistically lower than those in the sTPC group. The prognosis of patients with breast cancer and subsequent lung cancer of over 18 months was not significantly different than that of single lung cancer, which supported the profound appeal to increase the involvement of these two primary cancers in potential beneficial clinical trials. For patients with lung cancer and prior breast cancer of within 6 months and subsequent breast cancer of over 18 months, prognosis was improved relative to single lung cancer. Therefore, additional attention is needed to eliminate the potential bias may when these patients are recruited in the clinical trials.

Analysis of potential disparities in lung cancer clinical trial participation among Medicare beneficiaries.

e18548 Background: Disparities in clinical trial participation can mean disparities in medical advances, and disproportionate participation is an ethical issue even if differential results are not expected. The disparate impact of Covid-19 highlighted the importance of representativeness in trials aiming to prevent or treat disease. Previous analyses suggest there are likely significant differences in cancer clinical trial participants by race, ethnicity, and age. However, these analyses generally compare trial demographics to broad population demographics. Methods: This analysis used the SEER-Medicare linked database with claims data from 2014-2016 to compare lung cancer clinical trial participants to similar lung cancer patients not participating in a treatment trial. We compared the race, ethnicity, sex, age, and number of comorbidities for Medicare beneficiaries with at least one claim for an active treatment for lung cancer to the demographics of Medicare beneficiaries with at least one claim coded with the National Clinical Trials (NCT) number for an active treatment trial in lung cancer. The relationship between clinical trial participation and demographic variables was assessed using chi-square tests for binary variables and t-tests for continuous variables and corrected for multiplicity. A logistic regression model was used to assess robustness of these findings. Clinical trial participants were hypothesized to be more likely to be White, non-Hispanic, and male, and have a lower mean age and fewer comorbidities than the comparable non-trial active treatment population. Results: We compared 1,624 lung cancer clinical trial patients to 34,077 active treatment lung cancer patients. Clinical trial participants were more likely than non-trial active treatment patients to be female (53.6% vs. 50.4%, p = 0.015) or Asian/Pacific Islander (13.0% vs. 5.2%, p < 0.001) and less likely to be Black (5.2% vs. 9.0%, p < 0.001) or White (76.5% vs. 81.4%, p < 0.001). Trial participants had a lower mean age (70.7 vs. 73.7, p < 0.001) and fewer comorbidities (3.0 vs. 4.6, p < 0.001). There was not a significant difference by Hispanic ethnicity (5.2% vs. 4.4%, p = 0.106). The regression analyses supported these findings. Conclusions: Most analyses of clinical trials enrollment do not have a direct comparison group. Because this study is directly comparing lung cancer trial participants and non-participants from the same Medicare beneficiary population, the results fill a gap in our understanding of disparities in cancer clinical trial participation. Trial participants in this analysis were more representative than hypothesized, although the results supported previous findings that Black patients and older patients are underrepresented in cancer trials. There was also lower participation by White patients. Underrepresentation of patients with comorbidities may be due to trial eligibility criteria.

Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo.

Lung cancer is the leading cause of cancer‐related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. However, the mechanism of luteolin on suppressing lung cancer growth is still unclear. We found that luteolin targeted LIMK1 from the in silico screening and significantly inhibited the LIMK1 kinase activity, which was confirmed with pull‐down binding assay and computational docking models. Treatment with luteolin inhibited lung cancer cells anchorage‐independent colony growth and induced apoptosis and cell cycle arrest at G1 phase. Luteolin also decreased the expression of cyclin D1 and increased the levels of cleaved caspase‐3 by down‐regulating LIMK1 signalling related targets, including p‐LIMK and p‐cofilin. Furthermore, luteolin suppressed the lung cancer patient‐derived xenograft tumour growth by decreasing Ki‐67, p‐LIMK and p‐cofilin expression in vivo. Taken together, these results provide insight into the mechanism that underlies the anticancer effects of luteolin on lung cancer, which involved in down‐regulation of LIMK1 and its interaction with cofilin. It also provides valuable evidence for translation towards lung cancer clinical trials with luteolin.

Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade

BackgroundCD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response...

ES19.05 Incorporating Patient Reported Outcomes into the Lung Cancer Registry

Coupled with advances in early detection, the rapid pace of innovation in lung cancer research is beginning to improve survival rates and extend lives for those diagnosed with lung cancer. Many more people are surviving with the disease long-term and facing new challenges (Vavala et al., Respirology, 2020). As survivorship increases, there is a growing imperative to more completely understand health-related quality of life issues that people with lung cancer are facing. This is compounded by the plethora of new treatment options – many of which do not yet have sufficient follow-up data to understand long-term side-effects and impacts on health and well-being. Patient reported outcomes are an essential part of understanding the true patient experience. Physician and patient reporting of symptomatic toxicities are often not concordant (DiMaio et al., Journal of Clinical Oncology, 2015). Incorporating patient reported symptom reporting into clinical workflow has even been demonstrated to not only reduce emergency department visits but to improve overall survival (Basch et al, Journal of Clinical Oncology, 2016). Real-world data sources like the Lung Cancer Registry (www.lungcancerregistry.org) provide access to thousands of patients globally that are living with lung cancer. Multiple studies have now been incorporated into the Lung Cancer Registry to demonstrate the feasibility and accessibility of collecting patient reported outcomes in a real-world setting as well as to better understand quality of life issues. An initial study examining the feasibility of collecting patient-reported outcomes from people diagnosed with lung cancer taking PD-1/PD-L1 immune checkpoint inhibitors in a real-world setting was performed in the Registry in 2018-2019 (Jim et al., manuscript submitted). This examination of 226 people revealed that 25% of patients experienced a treatment delay, 12% had an emergency room visit, and 9% were hospitalized due to toxicity. There was no significant difference in health-related quality of life events between the four immune checkpoint inhibitors examined. Notably, patients reported a lower overall health related quality of life, functional well-being, and emotional well-being compared to general population and cancer norms (Brucker et al., Eval Health Prof, 2005). Fatigue, aching joints, aching muscles, insomnia, shortness of breath, itching, and skin dryness were reported by more than half of study participants. These data indicate key areas of concern for those who are may be living long-term on or after treatment with immune checkpoint inhibitor therapy and underscore the importance of appropriate palliative and survivorship care. After confirming the feasibility of the immunotherapy study, the Lung Cancer Registry incorporated longitudinal tracking of patient-reported outcomes on a quarterly basis, starting in late November, 2019. Multiple stakeholders, including patients, caregivers, academic, and industry collaborators were consulted in the design of the questionnaires. After providing informed consent for an IRB-approved, observational research study, participants are asked about symptoms and side-effects every three months and complete the EORTC QLQ-C30 quality of life survey instrument (Aaronsen et al, J Natl Cancer Inst, 1993) as well as the EORTC LC-29 survey (Koller et al., Lancet Oncol, 2020). This data is coupled with patient-provided information about changes in cancer status (such as stage, recurrence, and biomarker testing) and information on treatment changes. Early analyses of these data show that the questionnaires are feasible and demonstrate expected trends, such as reduced physical functioning in stage IV patients currently taking first or second line chemotherapy compared to similar patients currently taking a targeted therapy or immunotherapy. Finally, the Lung Cancer Registry has partnered with a multidisciplinary team of investigators (including patients and patient advocates) to launch a landmark study on Women’s sexual health (https://www.iaslc.org/iaslc-news/ilcn/shawl-largest-study-its-kind-evaluates-sexual-dysfunction-women-lung-cancer). Initially prompted by patient experiences that were expressed to the principal investigator, this study utilizes PROMIS measures assessing sexual health (Flynn et al., J Sex Med, 2013) to understand sexual side effects after lung cancer treatment. To date, there is very little known on this topic. Clinical trials for new lung cancer therapeutics generally do not collect this information. The study will be actively accruing until the end of Q1 2021. The investigators aim to learn more about the problems being faced with the goal of providing effective management strategies in the future. Taken together, all of these studies underscore the need to learn directly from people living with lung cancer to ensure that we are effectively designing and implementing appropriate supportive care and side-effect management within clinical care pathways. Utilizing real-world sources such as registries to complement quality of life data being collected in lung cancer clinical trials will improve knowledge around toxicities and side-effects and can lead to new management strategics and overall improved well-being for those diagnosed with lung cancer. patient reported outcomes, quality of life, Survivorship

Symptom burden and willingness to participate: implications for herbal clinical trials in lung cancer.

Background:People with lung cancer are interested in using herbs for symptom management. However, well-designed clinical trials are lacking. We aimed to quantify symptom burden and willingness to participate in herbal clinical trials among this population.Methods:We conducted a cross-sectional analysis using data collected from people with lung cancer at an oncology clinic at an academic cancer center. The primary outcome was self-reported willingness to participate in herbal research. We measured symptoms using the MD Anderson Symptom Inventory (MDASI). Multivariate logistic regression was performed to explore the relationship between demographic/clinical factors, symptom burden, and willingness to participate in herbal studies.Results:Among 288 participants, 55% were female, 42% were >65 years, 54% had stage IV cancer, and 86% had non-small cell lung cancer (NSCLC). Nearly half (46%) indicated willingness to participate in an herbal clinical trial. The most commonly reported moderate to severe symptoms (≥4 on the MDASI scale) were fatigue (57%), drowsiness (44%), disturbed sleep (43%), distress (42%), and dyspnea (36%). In multivariate analyses, higher education was significantly associated with willingness to participate in herbal studies (adjusted odds ratio 1.87, 95% confidence interval, 1.12–3.10, P=0.016), while symptom burden was not.Conclusions:People with lung cancer experience high rates of symptom burden. Nearly half of our participants expressed willingness to participate in an herbal clinical trial, particularly those with higher education. These findings can inform the design of future herbal clinical trials targeting common symptoms in lung cancer populations.

Abstract PO-096: A guide for development of a successful and inclusive lung cancer research strategy based on U.S. best practices

Abstract Disparities in clinical research are well-documented, and part of the broader health care disparities we see as a byproduct of systemic and institutional racism. COVID-19 vaccine and treatment development has greatly amplified the need for all communities to have the same opportunity to participate in research. Lack of representation of minorities in lung cancer clinical trials have been reported over the past 20 years. We have previously reported that there is a disconnect between U.S. lung cancer clinical trials placement and where patients with lung cancer reside, especially racial minorities. Both NCCN and ASCO guidelines suggest that clinical trials be considered the standard-of-care for advanced-stage non-small cell lung cancer and extensive-stage small cell lung cancer patients in first- and subsequent- line settings. In addition, participation in clinical trials has been associated with improved overall survival in lung cancer regardless of cancer stage, insurance and other prognostic factors. In order to provide better outcomes and achieve health equity for historically underserved populations, we must work together with all stakeholders to increase representation of diverse populations in lung cancer research. Our Question: What is a successful and sustainable multi-stakeholder framework that will result in inclusive lung cancer research in the US? Our methods will expand on previous work in the identification of notable practices where the focus was on successful pan-cancer inclusive clinical trial practices in 8 US cancer centers. We will include notable practices and recommendations of all stakeholders and focus on successful lung cancer inclusive research practices including behavioral research, community-based research and clinical research. We will conduct a robust environmental scan to identify strategies and standards, process and capabilities and roles. We will specifically identify tools and references to engage patients with lung cancer where applicable and interview identified experts based on practice themes representing all key stakeholder groups. Authors have identified 14 preliminary practice themes representing all key stakeholder groups to guide our framework development: Leadership & Goals; Protocol development; Operations and process; Data collection standards and reporting; Site selection, Health literacy & translation of recruitment materials including informed consent; Bilingual research staff; Community & Patient Engagement; PCP engagement; Digital capablities, Budget elements; Employee engagement and training; IRB Approval; Investigator meeting standards. Our framework is intended deliver the foundation for a theoretical underpinning of a evidenced based practical guide toward fostering collaboration amongst and between health care systems, academia, industry, health care leaders, PCPs, and patient organizations to promote successful inclusive research practices in lung cancer and will provide a roadmap for other disease areas. Citation Format: Jeanne M. Regnante, Narjust Duma, Quita Highsmith, David E. Gerber, Lorna McNeill, Upal Basu Roy, Gerren Wilson, Mary Stober Murray, Andrea A. Ferris, Fabian Sandoval, Moon S. Chen, Jr. A guide for development of a successful and inclusive lung cancer research strategy based on U.S. best practices [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-096.

Histone Deacetylase Inhibition in Non-small Cell Lung Cancer: Hype or Hope?

Epigenetic modulation, including acetylation, methylation, phosphorylation, and ubiquitination, plays a pivotal role in regulation of gene expression. Histone acetylation—a balance between the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs)—is one of the key epigenetic events. Our understanding of the role of HDACs in cancer is evolving. A number of HDAC isoenzymes are overexpressed in a variety of malignancies. Aberrant histone acetylation is associated with dysregulation of tumor suppressor genes leading to development of several solid tumors and hematologic malignancies. Pre-clinical studies have demonstrated that HDAC-1 gene expression is associated with lung cancer progression. Histone hypoacetylation is associated with more aggressive phenotype in adenocarcinoma of the lung. HDAC inhibitors (HDACi) have pleiotropic cellular effects and induce the expression of pro-apoptotic genes/proteins, cause cellular differentiation and/or cell cycle arrest, inhibit angiogenesis, and inhibit transition to a mesenchymal phenotype. Consequently, treatment with HDACi has shown anti-proliferative activity in non-small cell lung cancer (NSCLC) cell lines. Despite promising results in pre-clinical studies, HDACi have shown only modest single agent activity in lung cancer clinical trials. HDAC activation has been implicated as one of the mechanisms causing resistance to chemotherapy, molecularly targeted therapy, and immune checkpoint inhibition. Therefore, there is a growing interest in combining HDACi with these agents to enhance their efficacy or reverse resistance. In this paper, we review the available preclinical and clinical evidence for the use of HDACi in NSCLC. We also review the challenges precluding widespread clinical utility of HDACi as a cancer therapy and future directions.

Multiorgan Immune-Related Adverse Events During Treatment With Atezolizumab.

Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti-PD-L1 inhibitors. A post hoc pooled analysis was conducted using individual patient data from atezolizumab monotherapy arms of 4 non-small cell lung cancer clinical trials. Incidence, clinical patterns, outcomes, and risk factors were investigated of selected organ-specific and multiorgan irAEs during treatment using the anti-PD-L1 inhibitor atezolizumab. From a total of 1,548 patients, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were the most common (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs. A total of 84 patients (5.4%) had multiorgan irAEs, 70 had 2, 13 had 3, and 1 had 4 different organs affected. "Skin plus" or "laboratory plus" were the most common irAE multiorgan clusters. Patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. Multiorgan irAEs were also associated with improved overall survival (hazard ratio, 0.47; 95% CI, 0.28-0.78; P<.0001) but not with progression-free survival (hazard ratio, 0.92; 95% CI, 0.62-1.35; P=.74) compared with the cohort with no irAEs. Multiorgan irAEs occurred in 5.4% of patients treated with atezolizumab in non-small cell lung cancer trials. Future trials should consider routine reporting of data on multiorgan toxicities in addition to organ-specific toxicities.

Abstract 1027: Inhibition of c-MET upregulates PD-L1 related immune escape in lung adenocarcinoma

Abstract Non-small cell lung cancer (NSCLC) patients with c-MET dysregulation may benefit from c-MET inhibitors therapy as inhibition of c-MET activity has emerged as a therapeutic approach against this disease. Although several c-MET inhibitors have been evaluated in phase III clinical trials in lung cancer, their benefits so far have been modest. Thus, furthering our understanding of the mechanisms contributing to the lack of success of c-MET inhibitors in clinical trials is essential toward the development of rational and effective combination strategies. Here we show that exposure of NCSLC cell lines to c-MET inhibitor tivantinib increases their expression of PD-L1, which in turn causes cells to become more resistant to T-cell killing. Tivantinib upregulates PD-L1 in NSCLC cells in dose and time-dependent manner. Mechanistically, inhibition of c-MET suppresses p-GSK3-beta, leading to the stabilization of PD-L1. Collectively, our findings suggest a potential crosstalk between c-Met inhibition and immune escape and provide a rationale for the combination therapy of c-Met inhibitors and immune checkpoint blockade in NSCLC. Citation Format: Xian Sun, Chia-Wei Li, Wei-Jan Wang, Mien-Chie Hung. Inhibition of c-MET upregulates PD-L1 related immune escape in lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1027.

Abstract 6226: Sapanisertib interferes with the NRF2-mediated stress response to synergize with Obatoclax and extend AT/RT survival

Abstract Atypical teratoid rhabdoid tumors (AT/RT) are the most common malignant brain tumors of infancy, highly resistant to all therapies, and responsible for one of the greatest numbers of life years lost due to cancer. We have previously demonstrated that Sapanisertib combines synergistically with cisplatin to extend survival in AT/RT. To understand the mechanisms underlying this synergy and to identify further novel combination therapies to improve AT/RT survival, we performed RNASeq on AT/RT cell models 4 hours after Sapanisertib treatment. Pathway analysis revealed that Sapanisertib disrupts the NRF2-mediated stress response and apoptotic signaling pathway leading to a pro-death phenotype. Activating mutations in the NRF2 coding gene, NFE2L2, have been identified as a possible biomarker predicting Sapanisertib efficacy in lung cancer clinical trials. Short hairpin knockdown of NRF2 led to decreased expression of the anti-apoptotic proteins MCL-1, BCL-2, and BCL-xL suggesting that interfering with NRF2 may drive this pro-death phenotype in AT/RT. Obatoclax is a synthetic small molecule inhibitor of the BCL-2 family of proteins that was well tolerated in phase II clinical trials and readily crosses the blood brain barrier. Obatoclax treatment of NRF2 knockdown AT/RT cell models slows cell growth, induces high rates of apoptosis, and leads to increased oxidative stress compared to short hairpin scramble controls (cell viability assay, t-test p&amp;lt;0.05; ANNEXIN V cell sorting assay t-test p&amp;lt;0.05, MUSE oxidative stress assay t-test p&amp;lt;0.05). We treated AT/RT cell models with Sapanisertib and showed that treatment decreases expression of NRF2 and MCL-1 (western blot). Sapanisertib combines synergistically with Obatoclax to increase oxidative stress, slow cell growth, and increase apoptosis (MUSE oxidative stress assay ANOVA p&amp;lt;0.05; cell viability assay, ANOVA p&amp;lt;0.05; ANNEXIN V cell sorting assay ANOVA p&amp;lt;0.05, Compusyn model of synergy, CI&amp;lt;1.0). We next developed orthotopic mouse models of AT/RT using our luciferase-labeled CHLA06 and BT37 AT/RT cell models. We administered Sapinisertib and Obatoclax using mouse equivalent dosing to human clinical trials (Sapinisertib 6mg/kg oral weekly, Obatoclax 10mg/kg oral twice a week). Combination treatment was well tolerated and more than doubled median survival. Our data supports a new clinical trial combining Sapinisertib with Obatoclax to extend survival in AT/RT. Citation Format: Ashlyn Parkhurst, Sabrina Wang, Harpreet Kaur, Antje Arnold, Charles Eberhart, Eric Raabe, Jeffrey Rubens. Sapanisertib interferes with the NRF2-mediated stress response to synergize with Obatoclax and extend AT/RT survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6226.

Abstract D081: Geographic relationship between lung cancer clinical trial sites and patient prevalence and demographics in the Medicare Fee-for-service program

Abstract Racial and ethnic minority groups have low rates of inclusion in cancer clinical trials (CCTs). For example, African American patients comprise 5% of patients enrolled in CCTs that support US Food and Drug Administration approval of new drugs but represent 13.3% of the general US population. Though cancer is the leading cause of death for Asian Americans, only 3% of CCTs is composed of Asian American participants. With the promise and rise of precision medicine, it is critical that study populations in clinical research reflect the changing US demographics. Expanding access to health data and analytics empower stakeholders to better understand and advocate for equitable research and treatment access in cancer. Research question: To what extent does the current US CCT site placement for non-small cell lung cancer (NCSLC) and small cell lung cancer (SCLC) reflect the reality of lung cancer patient prevalence and demographics in the US? Methods: Researchers used the following two primary data sources: (1) Medicare Fee-for-Service (FFS) patient-level claims data from 2016, including the following data elements: prevalence, co-morbidities, hospital encounters, and costs for patients with ICD-10 codes for NCSLC and SCLC, by demographic (age, gender, race, and ethnicity). Locations were designated as high (greater than 0.87%) or low (less than 0.87%) prevalence, based on national average prevalence. (2) CCT placement data was sourced from 2018 Clinical Trials.gov to determine ongoing NCLSC and SCLC studies where there are US study sites. Data were mapped on the Lung Cancer Index™, a National Minority Quality Forum (NMQF) geographic information system (GIS) with an interactive data warehouse and data visualization system, including geomapping. Preliminary data conclusions: 1) Of the 2812 interventional CCTs, the study team mapped 495 therapeutic, interventional, currently enrolling CCTs (after excluding trials for behavioral interventions and palliative care). 2) Of the 10015 zip codes mapped, 58.8% of those were designated as zones of high prevalence (HP) of lung cancer. Of the 5888 HP zip codes, only 10.5% had NSCLC trials and 5.6% percent had SCLC trials. 3) When analyzed by counties, of the 59% of counties with high prevalence of African American patients, only 3% and 1% of counties had more than 10 NSCLC trials and 10 SCLC trials respectively. Similarly, of the 24% of counties with high prevalence of Asian American lung cancer patients, only 3% and 1% of counties had more than 10 NSCLC and 10 SCLC trials respectively. Implications: While additional analyses are ongoing, preliminary findings suggest that there is a major disconnect between US lung CCT placement and where patients live. The advent of precision medicine creates urgency to improve CCT enrollment of racial and ethnic minority groups, for equitable benefit of resulting innovation and access to optimal treatment. Lung cancer prevalence, including by population demographics, at the zip code and county level can be a critical guide to CCT site placement. Citation Format: Upal Basu Roy, Liou Xu, Laura Lee Hall, Gary Puckrein, Andrea Ferris, Jeanne Regnante. Geographic relationship between lung cancer clinical trial sites and patient prevalence and demographics in the Medicare Fee-for-service program [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D081.

Immunotherapy in Advanced Non-Small Cell Lung Cancer.

Traditionally, lung cancer has been treated as an immune-resistant disease with platinum-based chemotherapy serving as the first-line treatment for metastatic disease. The efficacy of immunotherapy has been established for patients with advanced lung cancer in clinical trials, and it has since become the standard of care for patients without targetable mutations, with or without chemotherapy. Previously, lung cancer patients experienced limited responses to immune-based therapy. As clinical trials continued to explore immunotherapy options with checkpoint inhibitors, results showed that immune therapies can create durable responses with manageable toxicities. Patients with advanced non-small cell lung cancer (NSCLC) can experience improved survival when administered immunotherapy over chemotherapy. The first successful immunotherapy treatments developed exploit programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), immune checkpoint pathways. Combination therapies of PD-1/PD-L1 inhibitors and chemotherapy or PD-1/PD-L1 and CTLA-4 checkpoint pathway inhibitors have also demonstrated improved outcomes for patients with NSCLC. Combination therapy with PD-1 or PD-L1 therapy and chemotherapy has shown benefit for small cell lung cancer patients as well. As immunotherapy changes the treatment paradigm of lung cancer, researchers continue to investigate different combinations, timing, duration, and biomarkers to better understand and improve the efficacy of immune-based therapy for patients with lung cancer.

Next Generation of Advanced Non-Small Cell Lung Cancer Therapy: Targeted and Immuno-Therapies

Lung cancer is one of the deadliest cancers in the world. Current clinical trials are focused on developing the next generation of therapies that target novel anti-cancer mechanisms. One approach is to prime the immune system, as the cancer has been known to suppress immune cells in the tumour microenvironment. Using pharmacotherapy, the immune system can be unleashed and suppress the cancer’s growth. Another pathway is targeting known oncogenic genes that are important for the cancer’s growth and survival. In lung cancer, the epidermal growth factor receptor and several other mutated proteins are targets of small-molecule inhibitors that have been shown to drastically improve patient survival and quality of life. Discussed in this review are broad highlights of the different immunotherapies and small molecule targeted therapies that have been studied in the latest clinical trials for lung cancer.

Expanding Access to Lung Cancer Clinical Trials by Reducing the Use of Restrictive Exclusion Criteria: Perspectives of a Multistakeholder Working Group

Low rates of adult patient participation have been a persistent problem in cancer clinical trials and have continued to be a barrier to efficient drug development. The routine use of significant exclusion criteria has contributed to this problem by limiting participation in studies and creating significant clinical differences between the study cohorts and the real-world cancer patient populations. These routine exclusions also unnecessarily restrict opportunities for many patients to access potentially promising new therapies during clinical development. Multiple efforts are underway to broaden eligibility criteria, allowing more patients to enroll in studies and generating more robust data regarding the effect of novel therapies in the population at large. Focusing specifically on lung cancer as an example, a multistakeholder working group empaneled by the LUNGevity Foundation identified 14 restrictive and potentially outdated exclusion criteria that appear frequently in lung cancer clinical trials. As a part of the project, the group evaluated data from multiple recent lung cancer studies to ascertain the extent to which these 14 criteria appeared in study protocols and played a role in excluding patients (screen failures). The present report describes the working group’s efforts to limit the use of these routine exclusions and presents clinical justifications for reducing the use of 14 criteria as routine exclusions in lung cancer studies, potentially expanding trial eligibility and improving the generalizability of the results from lung cancer trials.

Detection of tumor antigens and tumor-antigen specific T cells in NSCLC patients: Correlation of the quality of T cell responses with NSCLC subtype

Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients’ T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).

Advances in clinical trials of targeted therapy and immunotherapy of lung cancer in 2018.

There were many clinical studies on lung cancer in 2018. In particular, significant progress has been made in immunotherapy and targeted therapy. Whether in small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) have shown good results. For patients with specific gene mutations, the new generation inhibitors also showed good results in clinical trials. In this review, we summarize the clinical trials in lung cancer in 2018 and describe the progress and prospects for lung cancer therapies.

Quantitative Imaging Assessment for Clinical Trials in Oncology.

Objective radiographic assessment is crucial for accurately evaluating therapeutic efficacy and patient outcomes in oncology clinical trials. Imaging assessment workflow can be complex; can vary with institution; may burden medical oncologists, who are often inadequately trained in radiology and response criteria; and can lead to high interobserver variability and investigator bias. This article reviews the development of a tumor response assessment core (TRAC) at a comprehensive cancer center with the goal of providing standardized, objective, unbiased tumor imaging assessments, and highlights the web-based platform and overall workflow. In addition, quantitative response assessments by the medical oncologists, radiologist, and TRAC are compared in a retrospective cohort of patients to determine concordance. The TRAC workflow includes an image analyst who pre-reviews scans before review with a board-certified radiologist and then manually uploads annotated data on the proprietary TRAC web portal. Patients previously enrolled in 10 lung cancer clinical trials between January 2005 and December 2015 were identified, and the prospectively collected quantitative response assessments by the medical oncologists were compared with retrospective analysis of the same dataset by a radiologist and TRAC. This study enlisted 49 consecutive patients (53% female) with a median age of 60 years (range, 29-78 years); 2 patients did not meet study criteria and were excluded. A linearly weighted kappa test for concordance for TRAC versus radiologist was substantial at 0.65 (95% CI, 0.46-0.85; standard error [SE], 0.10). The kappa value was moderate at 0.42 (95% CI, 0.20-0.64; SE, 0.11) for TRAC versus oncologists and only fair at 0.34 (95% CI, 0.12-0.55; SE, 0.11) for oncologists versus radiologist. Medical oncologists burdened with the task of tumor measurements in patients on clinical trials may introduce significant variability and investigator bias, with the potential to affect therapeutic response and clinical trial outcomes. Institutional imaging cores may help bridge the gap by providing unbiased and reproducible measurements and enable a leaner workflow.

Publication Rate and Characteristics of Lung Cancer Clinical Trials

Publication Rate and Characteristics of Lung Cancer Clinical Trials

MA24.01 Challenges in Lung Cancer Clinical Trials: A European Perspective

MA24.01 Challenges in Lung Cancer Clinical Trials: A European Perspective