Unmet Needs, Quality of Life, and Financial Toxicity Among Survivors of Lung Cancer.

Importance: Despite a growing population of survivors of lung cancer, there is limited understanding of the survivorship journey. Survivors of lung cancer experience unmet physical, social, emotional, and medical needs regardless of stage at diagnosis or treatment modalities. Objective: To investigate the association of unmet needs with quality of life (QOL) and financial toxicity (FT) among survivors of lung cancer. Design, Setting, and Participants: This survey study was conducted at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center thoracic oncology clinics between December 1, 2020, and September 30, 2021, to assess needs (physical, social, emotional, and medical), QOL, and FT among survivors of lung cancer. Patients had non-small cell lung cancer of any stage and were alive longer than 1 year from diagnosis. A cross-sectional survey was administered, which consisted of an adapted needs survey developed by the Mayo Survey Research Center, the Comprehensive Score for Financial Toxicity measure, and the European Organization for Research and Treatment of Cancer QLQ-C30 QOL scale. Demographic and clinical information was obtained through retrospective medical record review. Data analysis was performed between May 9 and December 8, 2022. Main Outcomes and Measures: Separate multiple linear regression models, treating QOL and FT as dependent variables, were performed to assess the adjusted association of total number of unmet needs and type of unmet need (physical, emotional, social, or medical) with QOL and FT. Results: Of the 360 survivors of lung cancer approached, 232 completed the survey and were included in this study. These 232 respondents had a median age of 69 (IQR, 60.5-75.0) years. Most respondents were women (144 [62.1%]), were married (165 [71.1%]), and had stage III or IV lung cancer (140 [60.3%]). Race and ethnicity was reported as Black (33 [14.2%]), White (172 [74.1%]), or other race or ethnicity (27 [11.6%]). A higher number of total unmet needs was associated with lower QOL (ß [SE], -1.37 [0.18]; P < .001) and higher FT (ß [SE], -0.33 [0.45]; P < .001). In the context of needs domains, greater unmet physical needs (ß [SE], -1.24 [0.54]; P = .02), social needs (ß [SE], -3.60 [1.34]; P = .01), and medical needs (ß [SE], -2.66 [0.98]; P = .01) were associated with lower QOL, whereas only greater social needs was associated with higher FT (ß [SE], -3.40 [0.53]; P < .001). Conclusions and Relevance: The findings of this survey study suggest that among survivors of lung cancer, unmet needs were associated with lower QOL and higher FT. Future studies evaluating targeted interventions to address these unmet needs may improve QOL and FT among survivors of lung cancer.

Outpatient Embedded Palliative Care for Patients with Advanced Thoracic Malignancy: A Retrospective Cohort Study.

Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but also with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, and overall survival for patients, as well as cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association between outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic and inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association between outpatient embedded palliative care and inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day (USD 3807 vs. USD 4695, p = 0.024). Furthermore, patients who received outpatient embedded palliative care had lower hospital admissions within 30 days of death (O.R. 0.45; 95% CI 0.29, 0.68; p < 0.001) and a lower inpatient mortality rate (IRR 0.67; 95% CI 0.48, 0.95; p = 0.024). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

Lung Cancer Survivorship: Physical, Social, Emotional, and Medical Needs of NSCLC Survivors.

BACKGROUND: Newer therapies prolong survival for patients with lung cancer. Beyond extending survival, the needs of lung cancer (LC) survivors are poorly described. METHODS: We conducted a single-institution needs assessment survey of LC survivors alive ≥1 year from diagnosis. Needs were rated on a 5-point Likert scale for 4 domains (physical, social, emotional, and medical). Multiple regression models identified demographic or treatment characteristics associated with more needs in each category. A subset analysis of survivors with metastatic LC was performed. RESULTS: Of 360 patients approached, 235 surveys were completed. Among completed survey respondents, the median age was 69 years; most were female (62%), married (71%), and White (74%); and 41% had stage IV cancer. Finding support resources (34%) was the most common medical need. Fatigue (70%), sleep disturbance (60%), memory and concentration (57.5%), weakness (54%), and trouble breathing (51%) were physical needs affecting more than half of respondents. The most common social need was managing daily activities (42%). Emotional needs were highly prevalent, with 79% of respondents reporting a fear of recurrence and 74.5% reporting living with uncertainty. Multiple regression analysis identified that receipt of multiple lines of systemic therapy and lower household income were associated with higher physical and social needs. Younger age was associated with having a greater number of social and emotional needs. Similar results were found in the subset of survivors with metastatic disease at diagnosis. CONCLUSIONS: The needs of LC survivors are diverse across multiple domains. Several clinical and demographic factors are independently associated with higher numbers of patient-reported needs. Our study identifies critical gaps in survivorship care for LC survivors with all stages of disease and highlights areas of future intervention.

Association of area-level mortgage denial and guideline-concordant non-small-cell lung cancer care and outcomes in the United States.

BACKGROUND: Racial and socioeconomic disparities in receipt of care for non-small-cell lung cancer (NSCLC) are well described. However, no previous studies have evaluated the association between mortgage denial rates and receipt of timely and guideline-concordant care for NSCLC and patient outcomes. METHODS: We identified individuals ≥18 years diagnosed with NSCLC between 2014 and 2019 from the National Cancer Database. Using the Home Mortgage Disclosure Act database, we calculated the proportion of denied home loans to total loans at the zip-code level and categorized them into quintiles. Our outcomes included receipt of guideline-concordant care based on clinical and pathologic stage at diagnosis and the National Comprehensive Cancer Network guidelines, time from surgery to chemotherapy initiation, and overall survival. RESULTS: Of the 629,288 individuals diagnosed with NSCLC (median age 69; IQR 61-76 years, 49.1% female), 47.8% did not receive guideline-concordant care. Residing in areas with higher mortgage denial rates and lower income was associated with worse guideline-concordant care overall (aRR = 1.28; 95% CI = 1.25-1.32) and for each cancer treatment modality, worse receipt of timely chemotherapy (aHR = 1.14; 95% CI = 1.11-1.17) and worse overall survival (aHR = 1.21; 95% CI = 1.19-1.22), compared with residing in areas with the lowest mortgage denial rate and highest income. CONCLUSIONS: Area-level mortgage denial rate was associated with worse receipt of timely and guideline-concordant NSCLC care and survival. This highlights the critical need to understand and address systemic practices, such as mortgage denial, that limit access to resources and are associated with worse access to quality cancer care and outcomes.

Improved lung cancer clinical outcomes in patients with autoimmune rheumatic diseases.

PURPOSE: Concomitant autoimmune rheumatic diseases (ARD) can add morbidity and complicate treatment decisions for patients with lung cancer. We evaluated the tumour characteristics at diagnosis and clinical outcomes in lung cancer patients with or without ARD. METHODS: This retrospective cohort study included 10 963 patients with lung cancer, treated at Johns Hopkins. Clinical data including tumour characteristics and outcomes were extracted from the cancer registry. Data on patients' history of 20 ARD were extracted from the electronic medical record. Logistic regression was used to compare tumour characteristics between those with and without ARD; Kaplan-Meier curves and Cox proportional hazards models were performed to compare survival outcomes. RESULTS: ARD was present in 3.6% of patients (n=454). The mean age at diagnosis was 69 (SD 10) and 68 (SD 12) in patients with and without ARD (p=0.02). Female sex and smoking history were significantly associated with a history of ARD (OR: 1.75, OR: 1.46, p<0.05). Patients with ARD were more likely to be diagnosed with stage 1 lung cancer (36.8% vs 26.9%, p<0.001) and with smaller tumour size (OR: 0.76, p=0.01), controlling for sex, race and histology. Notably, lung cancer patients with ARD had a significantly prolonged median overall survival (OS) (7.11 years vs 1.7 years, p<0.001), independent of stage. CONCLUSION: Patients with ARD and lung cancer had better OS compared with their counterparts, independent of cancer stage and treatments and were less likely to have advanced stage lung cancer at diagnosis. Additional studies are needed to investigate the differential immunological anti-tumour immune activity and genomic variations in patients with and without ARD.

Clinician Perceptions of Barriers and Facilitators for Delivering Early Integrated Palliative Care via Telehealth.

Early integrated palliative care (EIPC) significantly improves clinical outcomes for patients with advanced cancer. Telehealth may be a useful tool to deliver EIPC sustainably and equitably. Palliative care clinicians completed a survey regarding their perceptions of the barriers, facilitators, and benefits of using telehealth video visits for delivering EIPC for patients with advanced lung cancer. Forty-eight clinicians across 22 cancer centers completed the survey between May and July 2022. Most (91.7%) agreed that telehealth increases access to EIPC and simplifies the process for patients to receive EIPC (79.2%). Clinicians noted that the elderly, those in rural areas, and those with less-resourced backgrounds have greater difficulty using telehealth. Perceived barriers were largely patient-based factors, including technological literacy, internet and device availability, and patient preferences. Clinicians agreed that several organizational factors facilitated telehealth EIPC delivery, including technological infrastructure (85.4%), training (83.3%), and support from study coordinators (81.3%). Other barriers included systems-based factors, such as insurance reimbursement and out-of-state coverage restrictions. Patient-, organization-, and systems-based factors are all important to providing and improving access to telehealth EIPC services. Further research is needed to investigate the efficacy of telehealth EIPC and how policies and interventions may improve access to and dissemination of this care modality.

Real-World Outcomes and Prognostic Factors Among Patients with Advanced Non-Small Cell Lung Cancer and High PD-L1 Expression Treated with Immune Checkpoint Inhibitors as First-Line Therapy.

Background: Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50%. Methods: A retrospective cohort study was conducted using the US de-identified electronic health record-derived Flatiron Health aNSCLC database (January 1, 2018, to July 31, 2021) among patients with PD-L1 ≥50% initiating first-line ICIs with or without chemotherapy. A clinical trial-like sub-cohort was also identified with Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no brain metastases or other primary cancers. Kaplan-Meier methods were used to estimate time to treatment discontinuation, time to next treatment, progression-free survival and overall survival (OS) by ICI regimen (ICI+chemotherapy, ICI monotherapy) and PD-L1 expression (50-69%, 70-89%, 90-100%). Cox proportional hazard models were used to examine associations between ICI regimen, PD-L1 level, and OS, adjusting for baseline demographic and clinical variables. Results: A total of 2631 patients with aNSCLC initiating ICI+chemotherapy (n = 992) or ICI monotherapy (n = 1639) were included; median (Q1, Q3) age was 71 (63-78) years and 51.6% were male. The trial-like sub-cohort (n = 1029) generally had better outcomes vs. the overall cohort. Patients receiving ICI+chemotherapy generally had longer median OS vs. ICI monotherapy. Multivariable analyses showed no association between ICI regimen and OS among patients with PD-L1 70-89% (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.73-1.09) or 90-100% (HR: 0.91, 95% CI: 0.77-1.08), but patients with PD-L1 50-69% receiving ICI+chemotherapy had longer OS (HR: 0.80, 95% CI: 0.64-0.99). Conclusion: Outcomes in real-world clinical trial-like patients with aNSCLC approached those reported in pivotal ICI trials in high PD-L1 expressers. ICI monotherapy offers a potential alternative in patients with PD-L1 ≥70% while avoiding potential chemotherapy toxicity exposure; the benefits are less clear in patients with PD-L1 50-69%. Future studies should confirm these findings.

Clinical Features, Survival, and Burden of Toxicities in Survivors More Than One Year After Lung Cancer Immunotherapy.

INTRODUCTION: Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood. MATERIALS AND METHODS: We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs). Long-term irAEs were defined as ongoing irAEs lasting >1 year; burden of toxicity measures were based on percentage of days a patient experienced toxicity. Using linear and logistic regression, we evaluated association between demographics and disease characteristics with burden of toxicity. RESULTS: We identified 114 ICI survivors from 317 patients with aNSCLC. Half (52%) experienced an irAE of any grade, and 23.7% developed long-term irAEs. More ICI survivors with irAES in the first year had never smoked (P = .018) or received ICIs as frontline therapy (P = .015). The burden of toxicity in the first year significantly correlated with the burden of toxicity afterward (ρ = 0.72; P < .001). No patients with progressive disease had a high burden of toxicity, and they experienced 30.6% fewer days with toxicity than those with stable disease. Increased duration of therapy was associated with higher odds of experiencing toxicity. Half of ICI survivors with irAEs were still receiving treatment for unresolved irAEs at time of death or last follow-up. CONCLUSION: Significant proportions of ICI survivors have unresolved long-term toxicities. These data support a growing need to understand long-term toxicity to optimize management of those treated with ICIs.

Sex-specific differences in immunogenomic features of response to immune checkpoint blockade.

Introduction: The magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower response rates and decreased survival after ICI monotherapy. The mechanisms underlying this sex dimorphism in ICI response are unknown, and may be related to sex-driven differences in the immunogenomic landscape of tumors that shape anti-tumor immune responses in the context of therapy. Methods: To investigate the association of immunogenic mutations with HLA haplotypes, we leveraged whole exome sequence data and HLA genotypes from 482 non-small cell lung cancer (NSCLC) tumors from The Cancer Genome Atlas (TCGA). To explore sex-specific genomic features linked with ICI response, we analyzed whole exome sequence data from patients with NSCLC treated with ICI. Tumor mutational burden (TMB), HLA class I and II restricted immunogenic missense mutation (IMM) load, and mutational smoking signature were defined for each tumor. IMM load was combined with HLA class I and II haplotypes and correlated with therapeutic response and survival following ICI treatment. We examined rates of durable clinical benefit (DCB) for at least six months from ICI treatment initiation. Findings were validated utilizing whole exome sequence data from an independent cohort of ICI treated NSCLC. Results: Analysis of whole exome sequence data from NSCLC tumors of females and males revealed that germline HLA class II diversity (≥9 unique HLA alleles) was associated with higher tumor class II IMM load in females (p=0.01) and not in males (p=0.64). Similarly, in tumors of female patients, somatic HLA class II loss of heterozygosity was associated with increased IMM load (p=0.01) while this association was not observed in tumors in males (p=0.20). In females, TMB (p=0.005), class I IMM load (p=0.005), class II IMM load (p=0.004), and mutational smoking signature (p<0.001) were significantly higher in tumors responding to ICI as compared to non-responding tumors. In contrast, among males, there was no significant association between DCB and any of these features. When IMM was considered in the context of HLA zygosity, high MHC-II restricted IMM load and high HLA class II diversity was significantly associated with overall survival in males (p=0.017). Conclusions: Inherent sex-driven differences in immune surveillance affect the immunogenomic determinants of response to ICI and likely mediate the dimorphic outcomes with ICI therapy. Deeper understanding of the selective pressures and mechanisms of immune escape in tumors in males and females can inform patient selection strategies and can be utilized to further hone immunotherapy approaches in cancer.

Definitive Chemoradiation and Durvalumab Consolidation for Locally Advanced, Unresectable KRAS-mutated Non-Small Cell Lung Cancer.

BACKGROUND: Consolidation durvalumab immunotherapy following definitive chemoradiation (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. As therapeutic options for patients with KRAS-driven disease evolve, more understanding regarding genomic determinants of response and patterns of progression for durvalumab consolidation is needed to optimize outcomes. METHODS: We conducted a single-institutional retrospective analysis of real-world patients with locally advanced, unresectable NSCLC who completed CRT and received durvalumab consolidation. Kaplan-Meier analyses compared progression-free survival (PFS) and overall survival (OS) from start of durvalumab consolidation between patients with KRAS-mutated and non-mutated tumors. Fisher's exact test was used to compare rates of intrathoracic or extrathoracic progression. RESULTS: Of 74 response-evaluable patients, 39 had clinical genomic profiling performed. 18 patients had tumors with KRAS mutations, 7 patients had tumors with non-KRAS actionable alterations (EGFR, ALK, ERBB2, BRAF, MET, RET, or ROS1), and 14 patients had tumors without actionable alterations. Median PFS for the overall cohort was 16.1 months. PFS for patients with KRAS-mutated NSCLC was 12.6 months versus 12.7 months for patients with non-actionable tumors (P= 0.77, log-rank). Fisher's exact test revealed a statistically significantly higher rate of extrathoracic progression versus intrathoracic-only progression for patients with KRAS-driven disease compared to patients with non-actionable tumors (P= 0.015). CONCLUSION: Patients with KRAS-mutated NSCLC derived similar benefit from durvalumab as patients with non-actionable tumors. A higher rate of extrathoracic progression was also observed among the patients with KRAS-mutated NSCLC compared to patients with non-actionable tumors. This highlights the potential unmet needs for novel systemic therapies and surveillance methods for KRAS-mutated stage III NSCLC.

Disparities in Telemedicine Success and Their Association With Adverse Outcomes in Patients With Thoracic Cancer During the COVID-19 Pandemic.

Importance: Disparities in access to telemedicine were identified at the onset of the COVID-19 pandemic, but the consequences of these disparities are not well characterized. Objective: To investigate factors associated with successfully accessing and completing telemedicine visits and the association between telemedicine visit success and clinical outcomes among patients with thoracic cancer. Design, Setting, and Participants: This retrospective cohort study included patients who attended outpatient visits at the thoracic oncology division of Johns Hopkins Medical Institute in Baltimore, Maryland, from March 1 to July 17, 2020. Main Outcomes and Measures: Associations of age, sex, race, ethnicity, insurance status, marital status, zip code, type of cancer, cancer stage, and type of therapy with telemedicine visit success (defined as completed visits with synchronous audio-video connection) and of visit success status with changes in therapy and odds of emergency department and urgent care visits, hospitalizations, and death were assessed using χ2 and Fisher exact tests and are reported as odds ratios (ORs). Results: A total of 720 patients and 1940 visits with complete data were included in the analysis; the median patient age was 65.7 years (range, 54.7-76.7 years), and 384 (53.33%) were male. Of the 1940 visits, 679 (35.00%) were in person and 1261 (65.00%) were telemedicine. Of the telemedicine visits, 717 (56.86%) were successful and 544 (43.14%) were unsuccessful. Patients who were Black (OR, 0.62; 95% CI, 0.41-0.95), had Medicaid (OR, 0.38; 95% CI, 0.18-0.81), or were from a zip code with an elevated risk of cancer mortality (OR, 0.51; 95% CI, 0.29-0.90) were less likely to have successful telemedicine visits than to have unsuccessful visits. Patients with at least 1 unsuccessful telemedicine visit had higher likelihood of an emergency department (OR, 2.73; 95% CI, 1.42-5.22) or urgent care (OR, 4.50; 95% CI, 2.41-8.41) visit or hospitalization (OR, 2.37; 95% CI, 1.17-4.80). Similarly, patients who had no successful telemedicine visits and for whom more than 1 telemedicine visit was scheduled had a higher likelihood of an emergency department (OR, 3.43; 95% CI 1.80-6.52) or urgent care (OR, 4.24; 95% CI 2.24-8.03) visit or hospitalization (OR, 4.19; 95% CI 2.17-8.10). Patients with all successful telemedicine visits (OR, 0.52; 95% CI, 0.30-0.90) or only 1, unsuccessful visit (OR, 0.32; 95% CI, 0.13-0.75) had lower odds of death compared with patients seen in-person only. Starting a new therapy was associated with lower odds of having a telemedicine visit vs an in-person visit (OR, 0.49; 95% CI, 0.37-0.64) and higher odds of a successful telemedicine visit vs an unsuccessful telemedicine visit (OR, 1.90; 95% CI, 1.28-2.82). Conclusions and Relevance: In this cohort study, patients with thoracic cancer who were Black, had Medicaid, or were from a zip code with a high risk of cancer mortality had increased odds of unsuccessful telemedicine visits compared with their counterparts and unsuccessful telemedicine visits were associated with worse clinical outcomes compared with successful visits. These findings suggest that more work is needed to improve telemedicine access for disadvantaged patients.

An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation. Results: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15−14.89; p < 0.001). Conclusion: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.

Mutation status and postresection survival of patients with non-small cell lung cancer brain metastasis: implications of biomarker-driven therapy.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS: The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS: Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS: Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

INTRODUCTION: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development. METHODS: Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP-: did not develop CIP) was determined clinically. Generalized estimating equation-based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC. RESULTS: A total of 43 patients (34 CIP-, 9 CIP+) with 79 PFTs (59 CIP-, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP- group (95% confidence interval: -38.6 to -4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP- cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively. CONCLUSIONS: Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

Cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy and pembrolizumab monotherapy in first line treatment of NSCLC in the US - updated analyses with additional trial follow-up.

OBJECTIVE: Pembrolizumab + chemotherapy substantially extends life expectancy for metastatic non-small cell lung cancer (NSCLC) patients. Its cost-effectiveness (CE) was previously evaluated based on interim trial analyses (follow-up ∼1 year). The present analysis describes CE incorporating additional follow-up based on protocol-specified final trial analyses (1-1.5 years additional follow-up), from a US healthcare payer perspective. METHODS: A partitioned survival model is used to compare pembrolizumab + chemotherapy vs chemotherapy using data from the KN189 (non-squamous patients) and KN407 (squamous patients) clinical trials. An indirect treatment comparison vs pembrolizumab monotherapy is made for patient subgroups with PD-L1 TPS ≥50% and 1-49% based on data from the KN024 and KN042 trials. Efficacy, treatment utilization, health utility, and safety data are derived from trials and projected over 20 years. Costs for drugs, non-drug disease management, and adverse events are also incorporated. RESULTS: Overall, versus chemotherapy alone, pembrolizumab + chemotherapy is projected to increase life expectancy by 1.12 years (3.35 vs 2.23) and 0.67 years (3.17 vs 2.50) in non-squamous and squamous patients, respectively. Resultant ICERs ($158,030/QALY and $178,387/QALY) are below a US 3-times GDP per capita threshold ($195,000/QALY). ICERs vs chemotherapy also generally fall below the threshold within PD-L1 sub-groups (except in squamous PD-L1 < 1%, which may have differed due to small sample size) while ICERs vs pembrolizumab monotherapy in PD-L1 ≥ 50% and 1-49% sub-groups generally exceed it (except in squamous PD-L1 1-49%); largely a result of the higher drug acquisition cost of pembrolizumab + chemotherapy relative to differences in life expectancy. CONCLUSIONS: Taken together, with longer-term trial follow-up and in the context of prior literature, in the US, one of the two options for pembrolizumab use (either pembrolizumab + chemotherapy or pembrolizumab monotherapy), represents a cost-effective treatment in virtually all non-squamous and squamous metastatic NSCLC patient populations and PD-L1 sub-groups evaluated.

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

Importance: Improved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness. Objective: To assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer. Data Sources: PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published from database inception through May 31, 2020, using predefined eligibility criteria within a PICOTS (population, intervention, comparator, outcome, timing, setting) format. Study Selection: Randomized clinical trials (RCTs), non-RCTs, and observational studies with a comparison group that evaluated benefits and/or harms and cohort studies that reported harms were selected. Data Extraction and Synthesis: Two reviewers independently screened studies for eligibility, serially abstracted data, independently assessed risk of bias, and graded strength of evidence (SOE). Main Outcomes and Measures: Benefits and harms of pharmacologic interventions were compared, focusing on breathlessness, anxiety, exercise capacity, and health-related quality of life. When possible, meta-analyses were conducted and standardized mean differences (SMDs) calculated. Results: In this systematic review and meta-analysis, a total of 7729 unique citations were identified, of which 19 studies (17 RCTs and 2 retrospective studies) that included a total of 1424 patients assessed the benefits of medications for management of breathlessness in advanced cancer or reported harms. The most commonly reported type of cancer was lung cancer. Opioids were not associated with more effectiveness than placebo for improving breathlessness (SMD, -0.14; 95% CI, -0.47 to 0.18) or exercise capacity ( SMD, 0.06; 95% CI, -0.43 to 0.55) (SOE, moderate); most studies examined exertional breathlessness. Specific dose and/or route of administration of opioids did not differ in effectiveness for breathlessness (SMD, 0.15; 95% CI, -0.22 to 0.52) (SOE, low). Anxiolytics were not associated with more effectiveness than placebo for breathlessness or anxiety (reported mean between-group difference, -0.52; 95% CI, -1.045 to 0.005) (SOE, low). Evidence for other pharmacologic interventions was limited. Pharmacologic interventions demonstrated some harms compared with usual care, but dropout attributable to adverse events was minimal in these short-term studies (range 3.2%-16%). Conclusions and Relevance: Evidence did not support the association of opioids or other pharmacologic interventions with improved breathlessness. Given that studies had many limitations, pharmacologic interventions should be considered in selected patients but need to be considered in the context of potential harms and evidence of an association of nonpharmacologic interventions with improved breathlessness.

Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy.

BACKGROUND: Definitive chemoradiation with consolidative immunotherapy offers the best chance for cure in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC). However, treatment-related lymphopenia (TRL) may negatively impact outcomes. METHODS: Patients definitively treated with chemoradiation and immunotherapy from 2015 to 2019 at a single tertiary academic center were identified. Severe lymphopenia was defined as <0.5 × 109 cells/L. Progression-free survival (PFS) was calculated by Kaplan Meier methodology. Univariate and multivariate Cox Proportional Hazard modeling was used to correlate clinical variables with disease outcome. Immune-related adverse events (irAEs) were assessed according to CTCAE version 5.0 criteria. RESULTS: Seventy-eight patients were included in the final cohort. The median age was 66 years (IQR: 58-73), 55 % were males, and 88 % had a KPS of >70. At baseline, 90 % (n = 70/78) of patients had a normal ALC and one patient had severe lymphopenia. After chemoradiation, the median ALC decreased from 1.52 × 109cells/L (IQR: 1.23-1.98) to 0.72 × 109cells/L (IQR: 0.52-0.94) (p < 0.001), 22 % (n = 17/78) of patients had a normal ALC, and 23 % (n = 18/78) of patients developed severe lymphopenia. Patients who initiated consolidative immunotherapy with severe lymphopenia had worse PFS than those who did not (median 217 days [IQR: 120-434] vs. 570 days [IQR: 401-NR], p < 0.001). On multivariate modeling, severe lymphopenia at the time of immunotherapy initiation remained an independent predictor of worse PFS (HR 4.90, p < 0.001). CONCLUSIONS: This is the first report to associate severe TRL with disease progression in patients with locally advanced NSCLC receiving consolidative immunotherapy. Factors associated with development of lymphopenia and strategies to mitigate lymphopenic effects should be considered.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear. METHODS: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020. FT was measured via the validated COmprehensive Score for financial Toxicity (COST) at the time of cancer diagnosis and at 6-month follow-up (6MFU). 6MFU data were compared with corresponding baseline data. A lower COST score indicates increased financial hardship. RESULTS: At the time of analysis, 215 agreed to participate. Subsequently, 112 patients completed 6MFU. On average, slightly more FT was observed at diagnosis compared with 6MFU (median COSTbase 25 v COST6M 27; P < .001); however, individual patients experienced large changes in FT. At 6MFU, 27.7% of patients had made financial sacrifices to pay for treatment but only 4.5% refused medical care based on cost. Median reported out-of-pocket (OOP) costs for the initial 6 months of cancer treatment was $2,496 (range, $0-25,900). Risk factors for FT at diagnosis were unique from risk factors at 6MFU. Actual OOP expenses were not correlated with FT; however, inability to predict upcoming treatment expenses resulted in higher FT at 6MFU. DISCUSSION: FT is a pervasive challenge during the initiation of lung cancer treatment. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, resulting in unique interventional targets throughout therapy.