Lung Cancer Symptom Scale Research Articles

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes

BackgroundIn CheckMate 9LA (NCT03215706), first-line nivolumab plus ipilimumab with chemotherapy (2 cycles) significantly improved overall survival versus chemotherapy (4 cycles) in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor/anaplastic lymphoma kinase alterations. We present exploratory patient-reported outcomes (PROs; minimum follow-up, 2 years). MethodsIn patients (N = 719) randomised 1:1 to nivolumab plus ipilimumab with chemotherapy or chemotherapy alone, disease-related symptom burden and health-related quality of life were assessed using the Lung Cancer Symptom Scale (LCSS) and 3-level EQ-5D (EQ-5D-3L). Treatment-phase changes in LCSS average symptom burden index (ASBI), LCSS three-item global index (3-IGI) and EQ-5D-3L visual analogue scale (VAS) and utility index (UI) over time were analysed descriptively and using mixed-effect model repeated measures. Time-to-deterioration/improvement analyses were conducted. ResultsTreatment-phase PRO questionnaire completion rates were >80%. Mean treatment-phase changes showed no deterioration from baseline in both arms for LCSS ASBI/3-IGI and EQ-5D-3L VAS/UI; however, minimally important differences were not met. Mixed-effect model repeated measures analyses showed overall reduction in symptom burden from baseline for both arms; changes from baseline for LCSS 3-IGI and EQ-5D-3L VAS/UI were numerically improved with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, but minimally important differences were not met. Nivolumab plus ipilimumab with chemotherapy delayed time-to-definitive-deterioration versus chemotherapy (LCSS ASBI: hazard ratio, 0.62 [95% confidence interval, 0.45–0.87]); results were similar across PRO measures. ConclusionsAt 2-year minimum follow-up, first-line nivolumab plus ipilimumab with chemotherapy reduced the risk of definitive deterioration in disease-related symptom burden and health-related quality of life versus chemotherapy and maintained QoL in patients with metastatic non-small cell lung cancer.Clinical trial registration: ClinicalTrials.gov Identifier, NCT03215706.

Assessing the impact of open-label designs in patient-reported outcomes: investigation in oncology clinical trials.

Knowledge of treatment assignment may affect patient-reported outcomes (PROs), which is of concern in oncology, where open-label trials are common. This study measured the magnitude of open-label bias by comparing PROs for similar patient groups in oncology trials with different degrees of concealment. Individual patient data from ipilimumab arms of 2 melanoma and docetaxel arms of 2 non-small cell lung cancer (NSCLC) trials were adjusted for differences using propensity score weighting. Patients were aware of treatment assignment in CA184-022 and CheckMate 057 (open-label) but not in MDX010-20 and VITAL (blinded). Overall survival (OS) and mean changes from baseline to week 12 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (melanoma) and Lung Cancer Symptom Scale (NSCLC) scores were compared between open-label and blinded groups. After adjustment, baseline characteristics were balanced between blinded (melanoma, n = 125; NSCLC, n = 424) and open-label (melanoma, n = 69; NSCLC, n = 205) groups. Study discontinuation and PRO completion rates at week 12 and OS were similar. There was no clear direction in differences in change scores between groups. In the melanoma trials, role functioning (mean = -5.2, 95% confidence interval [CI] = -15.4 to 5.0), global health status (mean = -1.3, 95% CI = -8.7 to 6.1), and pain (mean = 6.2 , 95% CI = -1.8 to 14.2) favored the blinded, whereas emotional functioning (mean = 2.2, 95% CI = -5.8 to 10.2) and diarrhea (mean = -8.3, 95% CI = -17.3 to 0.7) favored the open-label group. In the NSCLC trials, changes in dyspnea (mean = 5.4, 95% CI = -0.7 to 11.5) favored the blinded and changes in appetite (mean = -1.2, 95% CI = -8.1 to 5.7) favored the open-label group. None were clinically or statistically significant. This study adds to the growing evidence demonstrating that concerns regarding open-label bias should not prohibit the interpretation of large and meaningful treatment effects on PROs.

BRACHY: A Randomized Trial to Evaluate Symptom Improvement in Advanced Non-Small Cell Lung Cancer Treated With External Beam Radiation With or Without High-Dose-Rate Intraluminal Brachytherapy

Uncontrolled studies suggest that the addition of high-dose-rate intraluminal brachytherapy (HDRIB) to external beam radiation therapy (EBRT) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBRT in a multicenter randomized trial. Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBRT (20 Gy in 5 daily fractions over 1 week or 30 Gy in 10 daily fractions over 2 weeks) or the same EBRT plus HDRIB (14 Gy in 2 fractions separated by 1 week). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks after randomization. Secondary outcomes included improvement in individual symptoms, symptom-progression-free survival, overall survival, and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40% to 60% with a 2-sided α of .05 and 80% power. A total of 134 patients were randomized over 4.5 years: 67 to each arm. The study closed early owing to slow accrual. The mean age was 69.8 years, and 67% of patients had metastatic disease. At 6 weeks, 19 patients (28.4%) in the EBRT arm and 20 patients (29.9%) in the EBRT plus HDRIB arm experienced an improvement in lung cancer symptoms (P=.84). When limited to patients who completed the LCSS, percentages were 40.4% versus 47.6%, respectively (P=.49). Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBRT plus HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (P=.03). No significant differences were observed in progression-free or overall survival. Grade 3/4 toxicities were similar between groups. Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBRT for palliation of lung cancer symptoms.

Different Endotracheal Intubations for Non-Small Cell Lung Cancer Surgery: A Retrospective-Case-Matched Study on Postoperative Complications and Quality of Life.

Lung isolation and separation is still controversial in thoracic surgery. Preferences of the surgeon can drive the decision to use single- vs. double-lumen endotracheal intubation. We aimed to compare complications and quality of life (QOL) after radical lung cancer resection with a single-lumen tube (ST) and a double-lumen tube (DT) for patients with non-small cell lung cancer (NSCLC). A total of 309 patients who underwent radical lung cancer resection with video-assisted thoracoscopy-lobectomy were subsequently included in the study. Based on the type of endotracheal intubation tube used during surgery, we divided all the patients into a single-lumen tube group (ST-G) and double-lumen tube group (DT-G). Then, we applied propensity score matching (1:1) to balance the baseline characteristics between the two groups. The Analysis of Variance (ANOVA) of two-factor repeated measures data was performed to compare postoperative complications at three and six months after surgery and postsurgical QOL at baseline at one month, three months, six months, and twelve months. Within three months after surgery, patients in the ST-G presented less cough symptoms in Lung Cancer Symptom Scale (LCSS), lower cough symptom scores (CSS) (one month and three months, p < 0.05) and better performance of Leicester Cough Questionnaire (LCQ) scores in physical part (one month, three months and six months, p < 0.05) with better overall QOL (one month and three months, p < 0.05) than those in the DT-G. Patients with STs displayed less postoperative cough symptoms and higher overall QOL than those with DTs. Although DT is the gold standard for thoracic surgeries, we suggest that postoperative cough symptoms should be given sufficient attention by surgeons.

Efficacy of Intrapleural or Intrapericardial Injection of Single Bevacizumab in the Treatment of Lung Cancer-Mediated Malignant Effusion.

The usage of bevacizumab for malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE) has attracted increasing interest from researchers, but the precise ways of bevacizumab administration remain unknown. Patients with histologically or cytologically confirmed non-small-cell lung cancer (NSCLC) with MPE or MPCE were enrolled in the study and treated with a low dose of single bevacizumab (100 mg) intrapleurally or intrapericardially injected after the drainage of the effusions. The Lung Cancer Symptom Scale (LCSS), efficacy, and safety of drug administration were used as evaluation parameters in this study. The results indicated that lung cancer-related symptoms were significantly improved following treatment, compared with symptoms before the treatment (LCSS, score 494 ± 78 vs. score 377 ± 77, mean ± SD) (P < 0.001). Malignant effusions were well controlled, and the median time to progression (TTP) was 91 days and 111 days in MPE and MPCE, respectively. In addition, no severe side effects were observed, except in one patient with mild dizziness. In summary, the low dose of single bevacizumab (100 mg) with intrapleural or intrapericardial injection is effective and safe in the treatment of lung cancer-mediated malignant effusion, rapidly improving the malignant effusion-related symptoms and quality of life in patients with NSCLC.

A Pilot Mixed-Methods Study of Malignant Pleural Mesothelioma Symptoms.

To describe symptoms of malignant pleural mesothelioma (MPM), a rare cancer associated with a poor prognosis and significant symptoms, via a pilot mixed-methods study, because it is unclear whether MPM symptom assessment tools accurately characterize these symptoms. Participants with MPM were recruited from a large northeastern U.S. academic medical center with an interprofessional MPM program. A mixed-methods pilot approach was employed using the Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso) to quantitatively describe MPM symptoms and semistructured interviews to qualitatively capture these symptoms. Seven participants with MPM completed the LCSS-Meso and qualitative interviews. The five symptoms evaluated by the LCSS-Meso were confirmed as symptoms of MPM in participant interviews. However, the presence and severity of some symptoms were either under- or overestimated by the scale. Two additional symptoms, distress and sleep disturbance, also emerged from the qualitative interviews. Nurses caring for people with MPM should have a thorough understanding of common symptoms, but they must also explore additional symptoms that are meaningful to each patient.

Malignant pleural mesothelioma: treatment patterns and humanistic burden of disease in Europe

BackgroundMalignant pleural mesothelioma (MPM) is an aggressive and rare tumour with poor prognosis. Most patients are diagnosed with advanced disease and there is a paucity of data on the humanistic burden of MPM in terms of impact on health-related quality of life (HRQoL) and activity. This study examined real-world treatment patterns and humanistic disease burden of MPM in Europe.MethodsPhysicians abstracted demographic/clinical characteristics and treatment data from MPM-patient medical records; MPM patients self-completed a questionnaire including symptoms, 3-level-EQ-5D questionnaire and Visual Analogue Scale (VAS), Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso), and Work Productivity and Activity Impairment (WPAI) questionnaire.ResultsPhysicians (n = 171) abstracted data of 1390 patients; 767/1390 patients self-completed questionnaires. Patients were elderly with advanced, unresectable MPM. Treatment patterns followed guidelines with most (81%) patients receiving platinum+antifolate chemotherapy at first line (1 L). Maintenance treatment use was high (51.1%) despite no recommended maintenance therapies. Symptom burden was high and health states and HRQoL were poor at 1; declining further with progression. Overall mean (SD): LCSS-Average Symptom Burden Index score was 48.8 (19.3; n = 758); EQ-5D Utility Index score was 0.510 (0.349; n = 763); EQ-5D VAS score was 54.2 (20.3;n = 766); LCSS-3-Item Global Index score was 143.2 (64.5; n = 762); LCSS-normal activities score was 51.9 (24.6;n = 765); WPAI-activity impairment was 56.0% (23.2%; n = 737).ConclusionThe humanistic burden of MPM is high, despite treatments being prescribed as per available guidance. Treatments that delay progression and provide palliation of symptoms are most likely to improve/maintain HRQoL.

Examining the relationship between symptoms watched in lung cancer patients and illness perception.

To examine the relationship between the symptom experience of lung cancer patients and their illness perception of the disease. The descriptive and cross-sectional study was conducted from April to September 2015 at the Chemotherapy Treatment Centre of the Medicine Chest Diseases Clinic at the Ege University, Izmir, Turkey, and comprised lung cancer patients of either gender aged >18 years. Data was collected using a predesigned Patient Questionnaire as well as the standard Lung Cancer Symptom Scale, Illness Perception Questionnaire and Karnofsky Performance Scale. The patients' sociodemographic characteristics and data on their illness, the symptoms they experienced and the numerical and percentage distribution of the items on the illness perception scale, mean and standard deviation values were examined. Pearson Correlation analysis was used to examine the correlation between illness perception and Karnofsky Performance Scale scores and other variables. Of the 105 patients, 86(81.9%) were males, 86(81.9%) were married, 49(46.7%) were elementary school graduates, 101(96.2%) were unemployed, and 95(90.5%) were receiving chemotherapy. The overall mean age of the sample was 61.43±8.24 years, the period since diagnosis was 11.38±17.84 months, and the duration of chemotherapy was 4.28±2.37 months. The mean symptom burden score was 22.75±10.85 and the Lung Cancer Symptom Scale score was 22.75±10.85. The mean score of the type of illness domain was 5.53±2.12. The overall mean global quality of life score was 64.30±12.60. As the symptom burden experienced by the lung cancer patients increased, their perception of the illness became more negative, and the longer the cyclical periods and the period of diagnosis, the patients' control over their illness decreased.

First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743

ObjectiveIn CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). Materials and MethodsPatients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. ResultsCompletion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36–0.74]) and showed a trend in symptom delay versus chemotherapy. ConclusionsNivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.

EVALUATION OF QUALITY OF LIFE IN LUNG CANCER PATIENTS

There is a growing need to improve end-of-life care in cancer patients and to evaluate it through questionnaires is an important tool to assess its results. The aim of this study was to evaluate the effect of the palliative care in the quality of life, distressing symptoms and functional capacity of patients with primary lung cancer with locally advanced disease and metastatic disease in a university hospital. Thirty patients with lung cancer, previously treated with curative intention and submitted to a palliative treatment, were enrolled for this study. They were divided into three groups. The first group had 10 patients, who lived between 30 and 59 days after admittance, the second, 10 patients who lived between 60 and 89 days and the third, 10 patients who lived 90 days or more. Data collection regarding five stressing symptoms: anorexia, dyspnea, pain, fatigue, hemoptysis, and cough, was performed according to Lung Cancer Symptom Scale and Karnofsky Performance Status Scale. By observational inspection, “Appetite” and “Karnofsky Performance Status Scale”, improved; “pain" worsened and "quality of life" improved after palliative care, according to the patients. Physical, psychological, spiritual and social factors influence the symptoms of patients with cancer in later life. Treatment by palliative care can provide comfort for these patients.

Three-year follow-up and patient-reported outcomes from CheckMate 078: Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer

ObjectivesIn the phase 3 CheckMate 078 study, nivolumab prolonged overall survival (OS) and showed a favorable safety profile versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer (aNSCLC). However, long-term efficacy, safety, and health-related quality of life findings with second-line nivolumab are very limited in Asian patients with previously treated aNSCLC. Here, we report updated clinical data and patient-reported outcomes (PROs) from the phase 3 CheckMate 078 trial with a 3-year minimum follow-up. Materials and methodsPatients with aNSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or unacceptable toxicity. The primary endpoint was OS; secondary endpoints included objective response rate, progression-free survival, safety, and disease-related symptom deterioration assessed using the Lung Cancer Symptom Scale (LCSS) by Week 12. Additional PRO assessments were exploratory endpoints. ResultsAt ≥ 37.3 months follow-up, 3-year OS rates were 19% with nivolumab and 12% with docetaxel; 30% and 0% of responders remained in response for ≥ 3 years, respectively. Incidence of treatment-related adverse events occurring after 2 years was lower than during the first 2 years. No new treatment-related deaths were reported. By Week 12 of treatment, rates of disease-related symptom deterioration were 32% with nivolumab and 47% with docetaxel. Completion rates for PRO questionnaires were ≥ 80% in both arms. Clinically meaningful and sustained improvements in LCSS Average Symptom Burden Index scores and delayed time to first symptom deterioration were observed with nivolumab against docetaxel. ConclusionsAt 3 years, nivolumab continued to demonstrate survival benefit versus docetaxel, exhibiting improvements in disease-related symptoms and overall health status in a predominantly Chinese patient population with previously treated aNSCLC. No new safety signals were observed. These findings are similar to the global population.

FP14.12 Quality of Life and Subgroup Analysis in a Phase 3 Randomized Study of Ensartinib vs Crizotinib in ALK–Positive NSCLC Patients: eXalt3.

Ensartinib (X-396) is a novel second-generation ALK tyrosine kinase inhibitor (TKI). In a phase 3 study interim analysis, ensartinib showed statistically significant improvement of median PFS over crizotinib in patients with ALK+ NSCLC who were ALK TKI naive or received up to one prior chemotherapy line, including higher efficacy against brain metastases. Ensartinib was well tolerated, with low grade rash, pruritus, edema, and transaminitis as the most frequent treatment-related AEs. Here we plan to present subgroups analyses and the quality of life outputs of the phase 3 eXalt3 study (NCT02767804). Patients with locally tested ALK+ NSCLC (ITT population) were randomized 1:1 to ensartinib (225 mg QD orally) or crizotinib (250 mg BID orally). No crossover was allowed. Patients were stratified by prior chemotherapy, ECOG PS, brain metastases, and geographic region. The modified ITT (mITT) population was prespecified to include all centrally ALK+ patients by Abbott FISH test. The primary endpoint was blinded independent review committee (BIRC)–assessed progression-free survival (PFS; RECIST v.1.1). Secondary endpoints included overall survival (OS), overall response rate (ORR), and time to treatment failure (TTF) in the brain and patients reported outcomes (PRO). PRO data collection included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30). A linear mixed model for repeated measures was used to analyze change from baseline in the Global Health Status/Quality of Life subscale (GHS/QOL), with a change of greater than or equal to ten points deemed meaningful. Time to symptom deterioration will be presented. In total, 290 patients were randomized (ensartinib [n=143]; crizotinib [n=147]).Median age was 54.1 y, 26% of patients had prior chemotherapy, and 36% of patients had baseline CNS metastases (5% had prior brain radiotherapy). The mITT population included 247 patients (ensartinib [n=121]; crizotinib [n=126]). At the July 1, 2020, data cutoff, 139 BIRC-assessed PFS events (73%) occurred in the ITT population and 119 (63%) in the mITT population. Median PFS was 25.8 months with ensartinib vs 12.7 months with crizotinib (HR, 0.52; P=.0003 by log-rank test) with a median follow-up of 23.8 and 20.2 months in the ITT population. Median PFS was not reached with ensartinib vs 12.7 months with crizotinib in the mITT population (HR, 0.48; P=.0002 by log-rank test). New subgroup analyses in mITT for ensartinib showed a trend for higher efficacy by prior chemotherapy vs no chemotherapy (mPFS NR vs 25.8). Both global health status (GHS) as well as 5 functional and 9 symptom domains within EORTC QLQ-C30 had clinical meaningful improvement over time for ensartinib. Ensartinib delays the time to worsening of GHS with HR =0.83 (95% CI [0.57, 1.20]) vs crizotinib. Complete subgroup analyses (forest plot and multivariate analyisis) will be presented at the conference as well as OS updates. Comprehenive EORTC QLQ-C30 and Lung Cancer Symptom Scale scores will also be reported at the conference. In ALK+ NSCLC patients ensartinib represents a new option in first-line setting. QOLs data support its favorable safety profile. Relevant subgroups analyses to evaluate its clinical impact will be presented at the meeting.

First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1

IntroductionIn CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs). MethodsPatients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted. ResultsPRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy. ConclusionsNivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.

Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study

IntroductionWe examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM). MethodsJapanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019). ResultsThirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study. ConclusionsOur results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM.

Do Patients Regret Having Received Systemic Treatment for Advanced Non-Small Cell Lung Cancer: A Prospective Evaluation.

Thousands of patients annually receive treatment for advanced non-small cell lung cancer (NSCLC), but little is known about their views on the decision to receive that treatment, or regret. This trial prospectively evaluated the incidence of regret and whether baseline characteristics, patient decision-making parameters, or clinical progress early in the treatment course predicts regret. Patients receiving systemic treatment for advanced NSCLC completed every 3-week patient reported outcome (PRO) assessment using the electronic Lung Cancer Symptom Scale (eLCSS-QL), including the 3-Item Global Index (3-IGI; assessing overall distress, activities, and quality of life [QL]). A prespecified secondary aim was to determine the frequency of regret evaluated at 3 months after starting treatment. Patients were randomized to usual care or enhanced care (which included use of the DecisionKEYS decision aid). Of 164 patients entered, 160 received treatment and 142 were evaluable for regret. In total, 11.5% of patients and 9% of their supporters expressed regret. Baseline characteristics did not predict regret; regret was rarely expressed by those who had a less than 20% decline or improvement in the 3-IGI PRO score after two treatment cycles. In contrast, when asked if they would make the same decision again, only 1% not having a 20% 3-IGI decline expressed regret, versus 14% with a 3-IGI decline (p = .01). The majority of patients having regret were identified early using the PRO 3-IGI of the eLCSS-QL measure. Identifying patients at risk for regret allows for interventions, including frank discussions of progress and goals early in the treatment course, which could address regret in patients and their supporters. This report documents prospectively, for the first time, the incidence of treatment-related regret in patients with advanced lung cancer and outlines that risk of regret is associated with patient-determined worsening health status early in the course of treatment. Identifying patients at risk for regret early in treatment (before the third cycle of treatment) appears to be crucial. Counseling at that time should include a discussion of consideration of treatment change and the reason for this change.

Quality of life with adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant non-small-cell lung cancer: Results from the ADJUVANT (CTONG1104) study

ObjectivesHealth-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. Materials and methodsIn the phase III ADJUVANT trial, patients with completely resected, stage II–IIIA (N1–N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. ResultsAt baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75–63509.05, p = 0.019; LCSS, 1.13, 1.04–1.22, p = 0.003; TOI, 88.39, 4.40–1775.05, p = 0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42–0.90, p = 0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43–0.93, p = 0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33–0.77, p = 0.001). ConclusionAdjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II–IIIA (N1–N2), EGFR-mutant NSCLC.

1238P Quality of life with adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant non-small cell lung cancer: Results from the ADJUVANT (CTONG1104) study

Health-related quality of life (HRQoL) provides information for comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. In the phase III ADJUVANT trial (ClinicalTrials.gov, NCT01405079), patients with completely resected, stage II–IIIA (N1–N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS), and Trial Outcome Index (TOI) questionnaires. HRQoL dynamics, improvements, and time to deterioration were compared between groups. At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed three questionnaires. Baseline scores were balanced between groups. HRQoL fluctuated and gradually improved in both groups. Longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95% confidence interval [CI] 2.75–63509.05, p = 0.019; LCSS, 1.13, 1.04–1.22, p = 0.003; TOI, 88.39, 4.40–1775.05, p = 0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95% CI 0.42–0.90, p = 0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43–0.93, p = 0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33–0.77, p = 0.001). Adjuvant gefitinib is associated with better HRQoL than VP, supporting the use of this adjuvant therapy for this patient group.

Marvelous objective response of low dose radiotherapy plus ICIs for extended stage small cell lung cancer.

e21097 Background: Immune checkpoint inhibitors (ICIs) has limited efficacy with unsatisfactory objective response for extensive stage small cell lung cancer (ES-SCLC). In this respective study, efficacy and toxicities of low dose radiotherapy (LDRT) plus ICIs for pretreated failure ES-SCLC has been evaluated, and marvelous objective response has been observed. Methods: From March 2018 to Dec 2019, ten pretreated failure ES-SCLC patients received LDRT (8-20Gy/2-10f, BED10 9.5-24Gy) for lesions located in lung or other sites plus ICIs (Nivolumab, Pembrolizumab, Ipilimumab, Durvalumab, and Sintilimab) were enrolled. Two patients received concurrent chemotherapy of etoposide plus cisplatin or albumin-bound paclitaxel monotherapy. ICIs were given within 7 days after LDRT. Efficacy, toxicities, and lung cancer symptom scale (LCSS) scores were evaluated. Results: Thirteen lesions (ten located in lungs, and the others located in adrenal gland, axillary lymph node, and abdomen) received LDRT. The gross tumor volume and planning target volume were 32.56 cc-430.19cc and 73.74 cc-771.41 cc, respectively. Eleven lesions did not receive radiotherapy. The objective response rate (ORR) of whole patients was 90% (9/10). The ORR and disease control rate (DCR) of radiated lesions were 92.3% (12/13) and 100% (13/13), compared to 9.1% (1/11) and 18.2% (2/11) for no radiated lesions. Volume shrinkage rates (VSRs) of radiated lesions were 35.16% to 95.91% (13.75cc-277.02cc), and 61.5% (8/13) of radiated lesions reduced more than 80%. VSRs for radiated lesions with volume &gt; 100cc were 63.07% to 95.91% (122.38cc-277.02cc). LCSS improved significantly after treatment (465±13.02 vs. 380±17.8, p= 0.0013). Lymphocyte declined initially and then recovered in patients with disease not progressed, on the contrary, it declined continuously in patients with disease progressed. The most popular toxicities were lymphopenia (70%) and anemia (60%). Grade 3-4 toxicities included lymphopenia (40%), thrombocytopenia (20%), anemia (20%), and granulocytopenia (10%). Conclusions: LDRT might enhance the effectiveness of ICIs greatly for tumor lesions, and radiotherapy should be considered to be given initially for ES-SCLC received ICIs treatment.

A randomized trial of the electronic Lung Cancer Symptom Scale for quality-of-life assessment in patients with advanced non-small-cell lung cancer.

Improving health-related quality of life (hrqol) is a key goal of systemic therapy in advanced lung cancer, although routine assessment remains challenging. We analyzed the impact of a real-time electronic hrqol tool, the electronic Lung Cancer Symptom Scale (elcss-ql), on palliative care (pc) referral rates, patterns of chemotherapy treatment, and use of other supportive interventions in patients with advanced non-small-cell lung cancer (nsclc) receiving first-line chemotherapy. Patients with advanced nsclc starting first-line chemotherapy were randomized to their oncologist receiving or not receiving their elcss-ql data before each clinic visit. Patients completed the elcss-ql at baseline, before each chemotherapy cycle, and at subsequent follow-up visits until disease progression. Prospective data about the pc referral rate, hrqol, and use of other supportive interventions were collected. For the 95 patients with advanced nsclc who participated, oncologists received real-time elcss-ql data for 44 (elcss-ql arm) and standard clinical assessment alone for 51 (standard arm). The primary endpoint, the pc referral rate, was numerically higher, but statistically similar, for patients in the elcss-ql and standard arms. The hrqol scores over time were not significantly different between the two study arms. The elcss-ql is feasible as a tool for use in routine clinical practice, although no statistically significant effect of its use was demonstrated in our study. Improving access to supportive care through the collection of patient-reported outcomes and hrqol should be an important component of care for patients with advanced lung cancer.

Quality of life with second or third line nab-paclitaxel-based regimens in advanced non-small-cell lung cancer.

Aim: Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods: Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results: QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19-56% and 9-51% of patients, respectively. Conclusion: While QoL trends were promising, additional data are required to support these regimens in this setting.