Systemic Therapy For Lung Cancer Research Articles

Lung cancer treatment patterns and factors relating to systemic therapy use in Australia.

Systemic therapies for lung cancer are rapidly evolving. This study aimed to describe lung cancer treatment patterns in New South Wales, Australia, prior to the introduction of immunotherapy and latest-generation targeted therapies. Systemic therapy utilization and treatment-related factors were examined for participants in the New South Wales 45 and Up Study with incident lung cancer ascertained by record linkage to the New South Wales Cancer Registry (2006-2013). Systemic therapy receipt to June 2016 was determined using medical and pharmaceutical claims data from Services Australia, and in-patient hospital records. Factors related to treatment were identified using competing risks regressions. A total of 1,116 lung cancer cases were identified with a mean age at diagnosis of 72 years and median survival of 10.6 months. Systemic therapy was received by 45% of cases. Among 400 cases with metastatic non-small cell lung cancer, 51% and 28% received first- and second-line systemic therapy, respectively. Among 112 diagnosed with small-cell lung cancer, 79% and 29% received first- and second-line systemic therapy. The incidence of systemic therapy was lower for participants with indicators of poor performance status, lower educational attainment, and those who lived in areas of socioeconomic disadvantage; and was higher for participants with small-cell lung cancer histology or higher body mass index. This population-based Australian study identified patterns of systemic therapy use for lung cancer, particularly small-cell lung cancer. Despite a universal healthcare system, the analysis revealed socioeconomic disparities in health service utilization and relatively low utilization of systemic therapy overall.

Association Between First-Line Immune Checkpoint Inhibition and Survival for Medicare-Insured Patients With Advanced Non–Small Cell Lung Cancer

Immunotherapy is now a cornerstone of treatment for advanced non-small cell lung cancer (NSCLC), but its uptake and effectiveness among older patients outside clinical trials remain poorly understood. To understand treatment patterns and evaluate the overall survival associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients who have advanced NSCLC and Medicare coverage. This retrospective cohort study included Medicare-insured patients in the US aged 66 to 89 years who initiated first palliative-intent systemic therapy for lung cancer between January 1, 2016, and December 31, 2018. Survival follow-up continued through March 31, 2020. A total of 19 529 patients who had advanced lung cancer and were insured by a Medicare fee-for-service plan were included in the analysis. Regimens included pembrolizumab monotherapy (n = 3079), combined platinum-based drug (ie, cisplatin or carboplatin [hereinafter, platinum]) and pemetrexed disodium (n = 5159), combined platinum and a taxane (ie, paclitaxel, nab-paclitaxel, or docetaxel) (n = 9866), and combined platinum, pemetrexed, and pembrolizumab (n = 1425), as ascertained using Medicare claims from the Centers for Medicare & Medicaid Services. The primary outcome was overall survival, which was measured using the restricted mean survival time (RMST) with propensity score adjustment for clinical and sociodemographic characteristics. Median survival was also reported for comparison with outcomes from registrational trials. A total of 19 529 patients (54% male, 46% female; median age, 73.8 [interquartile range, 69.9-78.4] years) were identified for analysis. The uptake of pembrolizumab-containing regimens in the Medicare population was rapid, increasing from 0.7% of first-line treatments in the second quarter of 2016 to 42.4% in the third quarter of 2018. Patients who were older (≥70 years, 2484 [81%]), were female (1577 [51%]), and/or had higher Risk Stratification Index scores (highest quintile, 922 [30%]) were more likely to receive single-agent pembrolizumab than chemotherapy. After propensity score adjustment, pembrolizumab was associated with survival similar to platinum/pemetrexed (RMST difference, -0.2 [95% CI, -0.5 to 0.2] months) or platinum/taxane (RMST difference, -0.7 [95% CI, -1.0 to -0.4] months). Patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy also had adjusted survival similar to those receiving platinum/pemetrexed chemotherapy (RMST difference, 0.5 [95% CI, 0.1-0.9] months). The unadjusted median survival was 11.4 (95% CI, 10.5-12.3) months among patients receiving single-agent pembrolizumab, approximately 15 months shorter than observed among pembrolizumab-treated participants in the KEYNOTE-024 trial. The unadjusted median survival was 12.9 (95% CI, 11.8-14.0) months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, approximately 10 months shorter than observed among platinum/pemetrexed/pembrolizumab-treated participants in the KEYNOTE-189 trial. Immunotherapy has been incorporated rapidly into treatment for patients with advanced NSCLC. However, survival estimates in the Medicare population are much shorter than those reported in registrational trials. These results provide contemporary estimates of survival for older patients with advanced NSCLC treated in routine practice, facilitating patient-centered decision-making.

Optimal Management of Radiation Pneumonitis: Preliminary Findings of an International Delphi Consensus Study

Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) and systemic therapy for lung cancer; however, the optimal practice for diagnosis, management and follow-up remains unclear. We sought to establish expert consensus recommendations for RP management. Following literature review on RP, 9 open-ended questions related to knowledge, risk-reduction, diagnosis and treatment were generated for this first round of a consensus-building Delphi process. International leaders in multidisciplinary thoracic oncology were invited to participate (n = 31). Key statements regarding RP diagnosis and management were generated from responses to produce statements for Round 2. Participants will be solicited regarding agreement/disagreement with statements using a 5-point Likert scale. Subsequent rounds will seek consensus in areas that remain unresolved. For Round 1, a 74% response rate (n = 23; 12 radiation oncologists, 5 clinical oncologists, 6 respirologists) was achieved. Eighty-three percent of respondents were not aware of any guidelines for management of RP and 17% used local guidelines or expert review articles. Clinical history, exam and lab criteria (13 respondents) and imaging (15 respondents) were cited as used for diagnosis, and RTOG (9 respondents) and CTCAE grading (14 respondents) for assessment. Radiation-specific factors predictive of RP included irradiated lung volume (especially V20), dose, RT technique and location. The majority of clinical and radiation oncologists used motion management, image guidance and IMRT planning to achieve dosimetric constraints and minimize normal lung dose. Systemic therapy-related RP predictive factors included adjuvant or concurrent chemotherapy, immunotherapy (IO), and use of other pulmonotoxic medications. Patient-related predictive factors included lung function, autoimmune disease, age, performance status and smoking status. Majority of clinicians use risk stratification of patients in order to mitigate RP. Respondents uniformly agreed that steroid therapy is the mainstay of treatment for moderate to severe RP, with variability in the dosing and tapers used. A multidisciplinary management approach was favored by all, including radiation and medical oncologists, respirologists, thoracic radiologists and/or infectious disease or rheumatology specialists if indicated. The majority believe that IO will add complexity in identifying RP. Regarding additional measures to prevent RP in IO patients, respondents were split, with 50% taking additional measures and 50% not, though majority favored monitoring by oncologists during IO cycles and counseling patients on increased RP risk. Responses from international thoracic oncology experts highlight areas lacking consensus in the diagnosis and management of RP. These data will inform the next round of Delphi questions, with an aim of reaching consensus on this common issue.

Association of Cerebrospinal Fluid Tumor DNA Genotyping With Survival Among Patients With Lung Adenocarcinoma and Central Nervous System Metastases

Owing to the improvement of systemic therapies for lung cancer, patients live longer, but the incidence of central nervous system (CNS) metastases also increases. Cerebrospinal fluid (CSF) has been proven better than plasma to reveal unique genetic profiling of intracranial metastases. How genetic alterations in CSF are associated with the prognosis of this heterogeneous patient group remains elusive. To examine the association of molecular alterations in CSF with the survival of patients with a diagnosis of lung adenocarcinoma and CNS metastases. This retrospective cohort analysis of 94 patients with advanced lung adenocarcinoma and CNS metastases was conducted from July 1, 2016, to July 31, 2018. Patients' CSF samples were collected, and next-generation sequencing of CSF circulating tumor DNA was performed. The main outcome was survival after diagnosis with CNS metastases. Genotyping of CSF circulating tumor DNA was studied to examine its association with the clinical outcomes of patients with CNS metastases. Of the 94 patients (49 male; mean [SD] age, 53 [1] years) with lung adenocarcinoma and CNS metastases evaluated, 79 harbored an EGFR variant. The most common genes seen in CSF were EGFR (79 [84.0%]), TP53 (57 [60.6%]), MET (23 [24.5%]), CDKN2A (22 [23.4%]), MYC (20 [21.3%]), NTRK1 (19 [20.2%]), and CDK6 (15 [16.0%]). Cluster analysis identified 5 molecular subtypes of CNS metastases. Patients in cluster I had the shortest median survival after diagnosis of CNS metastases compared with each of the other clusters (cluster I, 7.5 months; cluster II, 55.7 months; cluster III, 17.9 months; cluster IV, 27.9 months; cluster V, 21.0 months) and significantly increased risk of death compared with patients in the other clusters (cluster II: hazard ratio [HR], 4.95; 95% CI, 1.50-16.41; P = .009; cluster III: HR, 4.75; 95% CI, 1.49-15.12; P = .008; cluster IV: HR, 6.38; 95% CI, 1.76-23.09; P = .005; cluster V: HR, 5.42; 95% CI, 1.63-17.98; P = .006). The genetic profiles of cluster I were characterized by a high detection rate of CDK4 (9 of 9 [100%]), TP53 (8 of 9 [88.9%]), MET (7 of 9 [77.8%]), and CDKN2A (7 of 9 [77.8%]). For those with EGFR variants, coalterations with CDK4 (HR, 2.02; 95% CI, 1.03-3.96; P = .04), CDK6 (HR, 2.52; 95% CI, 1.32-4.83; P = .005), and MYC (HR, 2.24; 95% CI, 1.21-4.15; P = .01) were associated with poor outcomes. Patients with a diagnosis of lung adenocarcinoma and CNS metastases experienced heterogeneous survival outcomes based on genetic profiling in CSF. These data suggest that CSF might facilitate risk stratifying CNS metastases into appropriate outcomes and provide reference for further clinical study.

Dietetic assessment and intervention in lung cancer.

Systemic therapy for lung cancer is increasing in intensity and duration. European nutrition guidelines suggest screening for weight loss and malnutrition, however acknowledges there is a lack of evidence. We discuss current data round this issue and identify opportunities for further research. International guidelines now exist to aid the definition of weight loss in cancer, including cachexia, sarcopenia and malnutrition. These allow consistent definition of overlapping, but distinct clinical syndromes. Nutritional status can be assessed in a range of ways including questionnaires, functional assessments, blood markers, physical activity, weight and BMI. Weight loss is commonly associated with a proinflammatory state. Future treatment is likely to be a combination of dietetic support and pharmacological treatment of cachexia. There is a paucity of data on dietetic intervention. It is potentially quick, inexpensive and patient specific, using a holistic approach to aid patients who are malnourished or at risk of malnutrition. Lung cancer-related weight loss is common, further strategies are needed to effectively assess and intervene. Dietetic intervention has the potential to improve patients' quality of life and outcomes.

30-day mortality after the start of systemic anticancer therapy for lung cancer: is it really a useful performance indicator?

Systemic treatment is the standard treatment for unresectable stage III and IV lung cancer. Nevertheless, a 5–10% death rate has been described within 30 days after the last systemic treatment, suggesting that these patient did not benefit. We analysed the 30-day mortality after start of systemic therapy.Data were retrieved from the Netherlands National Cancer Registry. From 2010 to 2015, 26 277 patients were included. 56% were men. The median age was 65 years and 31% of patients were aged ≥70 years. 27% involved small cell lung cancer and 73% nonsmall cell lung cancer. Overall mortality within 30 days after the start of systemic treatment was 6.2%. Multivariable analysis established the prognostic influence of age, histology, number of metastatic sites and type of systemic treatment. Chemotherapy was administered in 77 hospitals, treating each 15–161 lung cancer patients with systemic therapy annually. None of the hospitals had a significantly higher 30-day mortality according to hierarchical multivariable analysis, controlling for case-mix.In the Netherlands, the 30-day mortality rate after start of systemic therapy for lung cancer patients was comparable with earlier reports. Hospital volume did not influence the 30-day mortality rate. 30-day mortality rate is not a meaningful indicator to monitor quality of care.

MS21.02 Chemotherapy through the 21st Century

MS21.02 Chemotherapy through the 21st Century

PC05.07 Let's Not Forget Chemo-Regret

PC05.07 Let's Not Forget Chemo-Regret

Who treats lung cancer? Results from a global survey.

In most Western nations, the medical oncologist plays a significant role in the administration of systemic therapy for lung cancer. In Japan however, treatment for lung cancer has historically been provided by pulmonologists and thoracic surgeons. A comparison of the management of advanced disease between Japan and other nations has not been described. An online, self-administered, international survey was sent to 3907 active members of the American Society of Clinical Oncology. Eligible participants were degreed physicians who prescribed systemic agents for adult cancer treatment within the past five years. In total, 281 respondents answered the questions regarding management of lung cancer. Thorough analysis demonstrated that pulmonologists play a significant role in Japan and the Netherlands, where the role of oncologic specialists is not well established. Of note, all the respondents from the Netherlands reported that pulmonary medicine primarily manages systemic chemotherapy in stage IV, adjuvant chemotherapy, and targeted therapy. We found there are several nations where non-oncologic specialists play a critical role in the systemic treatment of lung cancer. We expect this practice pattern to continue until the global adoption of the oncologic specialty role.

Amenorrhea in lung cancer patients.

e20092 Background: More than 5,000 premenopausal women are diagnosed (dx’d) with lung cancer annually in the United States. Improvements in treatment are contributing to a growing population of young survivors. Limited data exist regarding the risk of treatment-related amenorrhea, a surrogate for infertility and early menopause, after systemic therapies for lung cancer. Methods: Since 1997, we mailed annual surveys to patients seen at Mayo Clinic for lung cancer who consented to join a research cohort. Surveys queried menopausal status and age of menopause. Those who were dx’d under age 50, who were treated with curative intent, and who reported that they were premenopausal at the time of the cancer dx were included in this analysis. “Immediate” treatment-related menopause was defined as reporting age of menopause as the same as the age at diagnosis or 1 year (yr) older. Results: Of 182 survey respondents to date (mean time from dx to 1st survey: 26 mos, SD 24 mos, range 12-202 mos), 85 (mean age 44 yrs, SD 5, range 34-48) received chemo during the yr after diagnosis, 26 of whom also received targeted therapy during that yr. Lung cancer dx occurred 1958-2016. Platinum drugs, taxanes, and etoposide were the most common chemotherapies. 46% of chemo recipients (mean age 47, SD 2, range 41-49) experienced immediate menopause, 9% (mean age 43 yrs, SD 5, range 35-48) experienced menopause at least 2 yrs after the age of dx, and 45% (mean age 40 yrs, SD 5, range 25-48) remained pre- or peri-menopausal at their final survey (on average 3 years after dx, SD 2, range 1-10). Only 3 patients received targeted therapy alone, and the remaining 94 (mean age 42 yrs, SD 6 years) received no systemic therapy within a year of diagnosis. 15% of these 94 (mean age 45 yrs, SD 3, range 41-49) experienced immediate menopause, 16% (mean age 43 yrs, SD 4, range 36-49) experienced menopause 2+ yrs after the age of diagnosis, and 69% (mean age 41 yrs, SD 7, range 20-49) remained pre- or perimenopausal at their final survey (on average 4 yrs after dx, SD 3, range 1-10). Conclusions: Chemotherapy for lung cancer causes amenorrhea in a substantial proportion of women dx’d with lung cancer while premenopausal. Further research on fertility and menopausal symptoms after lung cancer treatment, and on differences between regimens, is warranted.

The Influence of Histological Subtype in Predicting Survival of Lung Cancer Patients with Spinal Metastases

Introduction Lung cancer is one of the most common primaries responsible for spinal metastases. Recent advancements in systemic therapies for lung cancer have significantly improved the survival of patients with certain histological subtypes. Existing prognostic scoring systems have little to no prognostic value in lung cancer spinal metastases, and this may be due to the lack of consideration of lung cancer histology in their algorithms. Since prognostication plays a key role in the decision for operative management of spinal metastases, this study aims to analyze survival of lung cancer patients with spinal metastases according to different histological subtypes, to provide some guidance in making more informed surgical management decisions, better complementing recent medical oncologic advancements. Materials and Methods All patients with histologically confirmed lung cancer treated for spinal metastases at our institution between May 2001 and April 2012 were retrospectively reviewed. The primary outcome measure was survival from the time of diagnosis. Survival data was obtained from the National Registry of Diseases Office. Patient demographic variables, lung cancer histology and various modalities of oncologic treatment were evaluated. Univariate and multivariate cox regression analyses of were performed using Stata v.12. Statistical significance was defined as p < 0.05. Results Out of a total of 180 patients, 51 were treated surgically. The overall median survival time was 4.8 months, (range: 0.1–111.1 months). When subdivided according to histology, patients with non-small cell lung cancer (NSCLC) had a median survival of 5.2 (range: 0.1–111.1) months while patients with small cell lung cancer had a median survival of 2.4 (range: 0.1–11.9) months. Female gender ( p = 0.049), chinese ethnicity ( p = 0.040), NSCLC ( p < 0.001), treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy ( p < 0.001), treatment with platinum doublet chemotherapy ( p < 0.001), and local radiotherapy ( p = 0.070) for spinal metastases were all significant good prognostic factors upon both univariate and multivariate analysis. Surgery for spinal metastases itself did not significantly improve survival ( p = 0.147). Conclusions Female gender, chinese ethnicity, NSCLC, treatment with EGFR TKI therapy, treatment with platinum doublet chemotherapy, and local radiotherapy for spinal metastases are all independent favorable prognostic factors for patients with lung cancers spinal metastases. Profiling patients according to these factors should help guide decisions for surgical management of spinal metastases given that prognostic scoring systems are currently not predictive in this patient group.

Lung Cancer Brain Metastases.

Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

Discordance Between Conclusions Stated in the Abstract and Conclusions in the Article: Analysis of Published Randomized Controlled Trials of Systemic Therapy in Lung Cancer

Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail. RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ(2) tests and logistic regression were used to identify factors associated with discordance. From among 114 eligible RCTs identified (90 for non-small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body of the articles. Discordance was most common when the experimental arm was strongly supported in the abstract but not in the body of the article (nine of 11; 82%); however, the converse was much less common (two of 11; 18%; P < .001). Intraclass correlations for the two reviewers were ≥ 0.9. The discordances were found to be independent of trial-related factors. Conclusive statements in the abstract can differ from those in the full text. Clinicians should use caution when they consider making changes in their practice on the basis of reading only the abstract of a published RCT.

Academic and community PCPs underestimate benefits of systemic therapy for lung and breast cancer.

e16545 Background: In previous studies primary care physicians (PCP) under-appreciated systemic therapy for breast cancer (BC) and even more for lung cancer (LC). Lack of knowledge and a possible bias against lung cancer patients were suggested as potential causes. This study evaluates if the unawareness about beneficial systemic therapy persists in the era of targeted therapy, and if academic PCPs have a different perception than community PCPs. Methods: 3444 surveys were sent out, (printed 2,497, electronic 947) to 1,993 Family Medicine (57%) and 1,451 Internal Medicine MDs (43%), in academic (13%) and non-academic centers (87%). Case scenarios asked if respondents believed in the potential curative and palliative role of chemotherapy in the early and advanced stage of either lung cancer (LC) or breast cancer (BC). The study was testing a 20% difference in response rate between academic and non-academic MDs with a power of 80% and alpha of 5%. Results: 316 physicians (9.1%) responded, 89 academic MDs (28%), 227 non-academic MDs (72%). The rate of returned surveys was equal by specialty. PCPs believed less in curative systemic therapy for LC than BC (42% vs. 72.6%, (p&lt;0.001). PCPs believed less in systemic therapy to improve DFS for LC than BC (58.2% vs. 75.5%, p&lt;0.001). PCPs believed palliative chemotherapy can prevent symptoms and prolong life in advanced asymptomatic disease, 79.5% in LC and 84.6% in BC (ns). Half of the PCPs refer patients with symptomatic advanced disease to palliative care before seeing medical oncology, 50.8% in LC and 53.1% in BC (ns). Academic and community MDs responded in the same pattern for all scenarios (p&gt;0.5). Conclusions: Academic and community PCPs are very often not aware of the curative and palliative benefits of systemic therapy. This persistent lack of awareness by PCPs requires more educational effort by medical oncologists and academic institutions.

Systemic Therapy for Lung Cancer

Systemic Therapy for Lung Cancer

Pharmacoeconomics of Systemic Therapies for Lung Cancer

The purpose of this article is to review the economics of systemic therapies for the treatment of lung cancer. Lung cancer treatment is moderately expensive. The overall cost to society is significant given its high incidence. Most analyses in patients with small cell lung cancer focus on supportive care measures. The economics of chemotherapy in patients with advanced small cell lung cancer, as assessed in one study, shows alternating chemotherapy to be cost effective. Numerous economic analyses of chemotherapy in patients with non-small cell lung cancer (NSCLC) have been completed using varying methodologies in a number of countries. In patients with advanced NSCLC, third generation chemotherapy in the first-line setting can be administered within reasonable incremental cost effectiveness. Single-agent docetaxel chemotherapy in the second-line setting has also been shown to fall within a reasonable cost-effective range. Based on this review, systemic therapies for lung cancer are, for the most part, cost effective. Information on the cost-utility of systemic therapies is more limited. In a population of cancer patients with poor prognosis, the inclusion of quality indicators in the calculation of costs (i.e. cost-utility analyses) will be of great importance to refine our understanding of costs and benefits using a more global approach. Future economic analyses of adjuvant chemotherapy and novel targeted therapies will be of great interest.