Lung Cancer Symptom Scale Scores Research Articles

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.

Symptom Burden in Extensive Disease Small Cell Lung Cancer (ED-SCLC): A prospective, observational study in U.S. community practices.

196 Background: There is a paucity of data describing the effect of treatment on symptom burden and health status for patients with ED-SCLC receiving care in US community oncology centers. This study explores ED-SCLC patient-reported outcomes independently for either first-line (1L), second-line (2L) or third-line (3L) therapy. Methods: CA209-118 is a prospective observational study of adult patients with lung cancer, including patients with ED-SCLC, in 70 US community practices enrolled between 2014-2017. Participants completed the Lung Cancer Symptom Scale (LCSS) and Euro-QoL 5-D (EQ-5D) utility index and visual analog scale (VAS) at the start of 1L, 2L, or 3L treatment and at follow-up visits. The LCSS is summarized in 3 scales: LCSS total scale which ranges from 0 – 100, average symptom burden scale (ASBI) ranging from 0 – 100, and a three-item global scale (3-IGI) ranging from 0 – 300 (lower scores reflect reduced burden). The EQ-5D scale is a preference based measure of health status with higher scores reflecting better quality and ranges from 0 to 1.0 (index) or 0 – 100 (VAS). LCSS and EQ-5D values at 60 days were predicted in a repeated measures model for patients having a score at baseline and at least 1 follow-up. Results: The mean LCSS and EQ-5D scores at the start of each line of therapy and predicted 60 day change are presented in the table . 60-day improvement was observed only for appetite and cough in 1L. A slight declining trend was seen in 2L and 3L. Conclusions: Patients with ED-SCLC treated in the community reported a high symptom burden at the start of each line of therapy which did not diminish throughout 60 days of treatment. [Table: see text]

Efficacy and Safety of Ramucirumab With Docetaxel Versus Placebo With Docetaxel as Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Subgroup Analysis According to Patient Age in the REVEL Trial

IntroductionRamucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non–small-cell lung cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff. Patients and MethodsPatients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs). ResultsPatients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95% CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab were not as evident; after model adjustment for prognostic factors, OS and PFS HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03), respectively. Age analysis according to quintiles showed HRs favoring ramucirumab for all age groupings. LCSS scores and AEs did not considerably differ between age groups. ConclusionIn this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age.

Treatment outcomes by histology in REVEL: A randomized phase III trial of Ramucirumab plus docetaxel for advanced non-small cell lung cancer

ObjectivesRamucirumab, a recombinant human immunoglobulin G1 monoclonal antibody inhibiting vascular endothelial growth factor receptor-2, increased overall survival (OS) combined with docetaxel versus docetaxel alone in non-small cell lung cancer (NSCLC) in the REVEL trial. Pre-specified exploratory analysis examined efficacy and safety by histology. Materials and methods1253 patients with NSCLC were randomized to receive ramucirumab (10mg/kg; n=628) plus docetaxel (75mg/m2) or placebo plus docetaxel (n=625) after disease progression on or after platinum-based therapy, with or without bevacizumab or maintenance therapy. OS was analyzed using Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using an unstratified Cox proportional hazards model. Primary quality-of-life analysis was time to deterioration (TtD) of the Lung Cancer Symptom Scale (LCSS) scores using the Kaplan-Meier method and Cox regression. ResultsMedian OS for adenocarcinoma was 11.2 months for ramucirumab-docetaxel (n = 377) and 9.8 months for placebo-docetaxel (n=348); HR=0.83 (95% CI: 0.69–0.99). In squamous disease, median OS was 9.5 months for ramucirumab-docetaxel (n=157) versus 8.2 months for placebo-docetaxel (n=171); HR 0.88 (95% CI: 0.69–1.13). Median OS for other nonsquamous was 10.8 months for ramucirumab-docetaxel (n=74) and 9.3 months for placebo-docetaxel (n=78); HR=0.86 (95% CI: 0.59–1.26). Treatment-emergent adverse events were comparable between treatment arms across histologic subgroups. TtD for LCSS scores was similar between treatment arms in the nonsquamous and squamous subgroups. ConclusionREVEL demonstrated similar favorable efficacy and manageable safety for ramucirumab-docetaxel across histologic subgroups of NSCLC.

Burden, emotional distress and quality of life among informal caregivers of lung cancer patients: An exploratory study.

This study was conducted to explore the interrelationships among caregiver burden, emotional status and quality of life (QoL) in caregivers of lung cancer patients, and to identify whether caregiver burden and health status are associated with patient emotional status and QoL. Forty-three dyads of lung cancer patients and their caregivers were included for analysis. Caregiver-reported outcomes were measured by Caregiver Burden Scale (CBS), Caregivers Quality of Life Index-Cancer (CQOLC) and Hospital Anxiety and Depression Scale (HADS), while patient-reported outcomes were collected by HADS and Lung Cancer Symptom Scale (LCSS). The majority of the CBS and CQOLC scores were significantly higher in anxious and depressed caregivers than non-anxious and non-depressed caregivers (p<.01 or .05). Caregivers of depressed patients experienced significantly greater emotional distress than those of non-depressed patients (p<.01). Significantly positive associations were identified among most of the CBS, CQOLC and caregiver HADS scores. Patient LCSS scores were positively correlated with the CBS and caregiver HADS scores, and patient HADS scores were also positively related to caregiver HADS scores. The close interrelationships between caregiver and patient health outcomes provide evidence that lung cancer patients and their caregivers should be viewed as a unit in future supportive service models.

Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE)

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patient and Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.

Quality of life results from the phase 3 REVEL randomized clinical trial of ramucirumab-plus-docetaxel versus placebo-plus-docetaxel in advanced/metastatic non-small cell lung cancer patients with progression after platinum-based chemotherapy

ObjectivesREVEL demonstrated that ramucirumab+docetaxel (RAM+DTX) improved overall survival, progression-free survival, and objective response rate in patients with advanced/metastatic non-small cell lung cancer with progression after platinum-based chemotherapy. This analysis examined quality of life (QoL) as assessed by the Lung Cancer Symptom Scale (LCSS) and clinician-reported functional status. Materials and MethodsThe LCSS includes 6 symptom and 3 global items measured on a 0–100-mm scale; higher scores represent greater symptom burden. LCSS and ECOG PS data were collected at baseline, every 3-week cycle, the summary visit, and at the 30-day follow-up. LCSS total score and Average Symptom Burden Index (ASBI) were calculated. The primary analysis compared time to deterioration (TtD) between treatment arms for all individual items and summary scores, defined as increase from baseline by ≥15mm using the Kaplan-Meier method and Cox regression. TtD to ECOG PS ≥2 was analyzed. ResultsThere were 1253 patients randomized to receive RAM+DTX or placebo+docetaxel (PL+DTX). Across all assessments, LCSS compliance was approximately 75% and balanced across arms. The mean (SD) baseline LCSS total score was 27.3mm (17.08mm) on RAM+DTX and 29.6mm (17.59mm) on PL+DTX. At 30-day follow-up, mean (SD) LCSS total score was 32.0 (19.03) on RAM+DTX and 32.5 (19.87) on PL+DTX. The TtD for all LCSS scores was similar between treatment arms. Stratified HRs (95% CI) for LCSS total score and ASBI were HR=0.99 (0.81, 1.22), p=0.932 and HR=0.93 (0.75, 1.15), p=0.514 with approximately 70% of patients censored. TtD to PS≥2 was similar between treatment arms (HR=1.03 [95% CI: 0.85, 1.26], p=0.743) with approximately two-thirds of the patients censored. ConclusionIn addition to improvement of clinical efficacy outcomes demonstrated in REVEL, these results suggest that adding ramucirumab to docetaxel did not impair patient QoL, symptoms, or functioning.

First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial

BackgroundThe efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial. Patients and MethodsChemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G. EGFR mutation status was subsequently determined for 74 patients. The symptoms and QoL were assessed using the Lung Cancer Symptom Scale (LCSS). The time to worsening of symptoms (TWS) was analyzed using the Kaplan-Meier method. ResultsIn the overall population, the TWS was generally longer in the G group (n = 109) than in the PC/G group (n = 109) for the LCSS symptoms classified as treatment-related (loss of appetite, fatigue) and tumor-related (cough, dyspnea, hemoptysis, pain). In the subgroup of patients with wild-type EGFR, the TWS was generally longer in the PC/G group (n = 13) than in the G group (n = 8) for the tumor-related LCSS symptoms. ConclusionIn this study population clinically selected to respond to gefitinib, the LCSS scores were more favorable in the G group than in the PC/G group. Patients with wild-type EGFR tended to show greater improvement in tumor-related LCSS symptoms with chemotherapy than with gefitinib alone. These LCSS outcomes provide further evidence that patients with wild-type EGFR might not benefit from first-line treatment of advanced NSCLC with gefitinib.

A Phase II Trial of Erlotinib and Concurrent Palliative Thoracic Radiation for Patients With Non–Small-Cell Lung Cancer

BackgroundThe downstream signaling pathways of the epidermal growth factor receptor might influence radiation resistance. Data from preclinical work support the hypothesis that erlotinib concurrent with radiation therapy (RT) might increase cancer cell killing. The present trial was designed to examine the efficacy and toxicity of combined erlotinib and palliative chest thoracic RT in non–small-cell lung cancer (NSCLC). Materials and MethodsPatients with newly diagnosed stage III-IV (American Joint Committee on Cancer, version 6) or recurrent NSCLC received 3 weeks of erlotinib at a dose of 150 mg daily, starting 1 week before palliative thoracic RT to 30 Gy in 10 fractions within 2 weeks. The primary outcome was a change in the quality of life, as measured by the Lung Cancer Symptom Scale (LCSS) question on the “symptoms of lung cancer” from baseline to 4 weeks after treatment. ResultsA total of 40 patients were recruited from 2 institutions. Of the 40 patients, 22 (55%) were men, with an average age of 71 years, and 60% had stage IV disease. A total of 26 patients (65%) completed the full course of erlotinib, and 35 (88%) completed the planned RT. Twenty-five patients (62.5%) reported LCSS scores at 4 weeks after treatment, with an average change (improvement) of −12.5 U (95% confidence interval, −23.0 to −1.9; 2P = .023). This was less than the a priori hypothesis of a change of −17.5 U. The median overall and progression-free survival was 5.2 and 3.2 months, respectively. ConclusionThe present single-arm, phase II trial did not demonstrate additional symptomatic benefit from concurrent erlotinib therapy with standard palliative thoracic RT for patients with locally advanced or metastatic NSCLC.

Quality of Life (Qol) Results from the Phase 3 Revel Study of Ramucirumab + Docetaxel (Ram + Dtx) Versus Placebo + Docetaxel (Pl + Dtx) in Advanced/Metastatic Nsclc Patients (Pts) with Progression After Platinum Based Chemotherapy

ABSTRACT Aim: RAM + DTX significantly improved overall survival and progression-free survival in pts with locally advanced or metastatic NSCLC with progression after platinum based chemotherapy. QoL data was obtained. Methods: Lung cancer symptom scale (LCSS) includes 6 symptom questions (loss of appetite, fatigue, cough, dyspnea, hemoptysis, pain) and 3 global items (symptom distress, difficulties with daily activities, global QoL) measured on a 0-100 mm scale, with higher scores representing greater symptom burden. LCSS and ECOG performance status (PS) data were collected at baseline (BL), every cycle, and at 30-day follow up (FU). LCSS total score and average symptom burden index (ASBI) were calculated. The primary prespecified analysis was time to deterioration (TtD) of the LCSS defined as increase from BL by ≥15 mm using the Kaplan-Meier method. TtD to PS ≥ 2 was also analysed. Results: Of the 1253 pts randomized to receive RAM + DTX or PL + DTX, 66.6% were male, median age was 62, and 67.4% had PS1. Pt compliance with LCSS was approximately 75% and balanced across both arms. The mean BL LCSS total score was 27.3 (SD 17.08) and 29.6 (SD 17.59) on RAM + DTX and PL + DTX, respectively. During treatment, the symptom burden appeared similar between treatment arms. At 30-day FU, mean total LCSS score was 32.0 (SD 19.03) and 32.5 (SD 19.87) on RAM + DTX and PL + DTX, respectively, reflecting a similar increase in symptom burden for both arms (mean increase of 5.4 and 6.0 from BL, respectively). The TtD for all LCSS scores was similar between treatment arms. Stratified HRs (95% CI) for LCSS total score and ASBI were HR = 0.99 (0.81, 1.22), p = 0.932 and HR = 0.93 (0.75, 1.15), p = 0.514 with approximately 70% of pts censored. TtD to PS ≥ 2 was similar between treatment arms (HR = 1.03; [95% CI: 0.85, 1.26], p = 0.742) with approximately two-thirds of the pts censored. Conclusions: In addition to the improvement of clinical outcomes demonstrated in REVEL, the primary QoL analyses suggest that there was no detriment in QoL and pt functioning by adding RAM to DTX second line chemotherapy. Disclosure: K. Park: Advisor - AVEO, Astellas, BI, Astra Zeneca, Clovis, Daiichi Sankyo, Eli Lilly, Roche; M. Thomas: I Receive speakers and AD-Board Honoraria from Lilly Roche BMS AD-Board Honoraria from AstraZeneca Novartis Pierre Fabre; S. Yurasov: I am a full time employee of Ely Lilly & Co. the Sponsor of this clinical study; A. Zimmermann: I am an employee of Eli Lilly and do own stock in Lilly; G. Cuyun Carter: Employee and stockholder of Eli Lilly and Company; M. Reck: Member of Adboard (compensated): Hoffmann-La Roche, Lilly, BMS, Pfizer, Novartis, Boehringer-Ingelheim, AstraZeneca Honoraria for lectures: Hoffmann-La Roche Lilly, BMS, Pfizer, Novartis, Boehringer-Ingelheim, AstraZeneca; M. Perol: Advisory Board for Roche. All other authors have declared no conflicts of interest.

A clinical study of single-agent gemcitabine versus gemcitabine plus Oxaliplatin in untreated elderly advanced nonsmall cell lung cancer

Objective To investigate the effect of two chemotherapeutic regimens suitable for elderly ad -vanced non-small cell lung cancer（NSCLC）.Methods A total of 58 elderly advance nonsmall cell lung cancer pa-tients randomized into two group：single-agent group and combined group .Single-agent group received gemcitabine 1 000mg/m2 at Days 1 and 8 for a 21 day cycle.Combined group received gemcitabine 1 000mg/m2 at Days 1 and 8 in combination earboplatin AUC 5 at Day 2 for a 21 day cycle .All patients in the two groups received 3 cycles of chemotherapeutic regimens.Results Of the single-agent group,complete remission （CR） in 1 cases,partial remis-sion （PR） in 12 cases, the effective rate was 46.4%,and of the combined group,CR in 1 cases,PR in 13 cases,the effective rate was 50.0%,there was no statistically significant difference between the two groups （P>0.05）.Of the single-agent group,the median survival time was 9.7 months,1-and 2-year survival rates were 31.3%,12.5%,re-spectively,and of the combined group ,the median survival time was 10.1 months,1-and 2-year survival rates were 33.8%,15.6%,respectively,there were no statistically significant difference between the two groups （χ2 =1.743, 1.529,1.739,all P>0.05）.The leutropenia and thrombocytopenia incidence of 3 to 4 grade in the combined group was 50.0%,46.4%,respectively,which were significantly higher than 28.6%and 18.0%in the single-agent group （χ2 =4.41,4.69,all P<0.05）.Lung Cancer Symptom Scale scores showed：after the treatment,the anorexia,fatigue and pain scores of the single-agent group improved significantly compared with pre-treatment （ t =2.687,2.789, 2.603,all P<0.05）,whereas no significant improvement in the combined group;After the treatment,three symptom scores of the single-agent group were significantly higher than those of the combined group （t=2.986,3.569,2.764, all P<0.05）.Conclusion Single-agent gemeitabine regimen efficacy is comparable with that of combined regimen for elderly advanced NSCLC with less adverse effects . Key words: Oxaliplatin; Gemcitabine; Carcinoma,Non-small-cell lung carcinoma; Aged

Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study

Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here. After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m(2) every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804. Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59-0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34-0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017). Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy. Eli Lilly.

A psychometric analysis of quality of life tools in lung cancer patients who smoke

Lung cancer is the leading cause of cancer death for both men and women in the United States. Patient quality of life (QOL) prior to cancer treatment is known to be a strong predictor of survival and toleration of treatment toxicities. A lung cancer patient's self-assessment of QOL is highly valued among clinicians as it guides treatment-related decisions and impacts clinical outcomes. Smokers are known to report a lower QOL. Limited research has been conducted on QOL outcomes in lung cancer patients who continue to smoke. To assess QOL, a reliable and valid QOL measure specific to lung cancer is required. The functional assessment of cancer therapy-lung cancer (FACT-L) and lung cancer symptom scale (LCSS) are instruments that specifically examine QOL among lung cancer patients. The LCSS is a focused QOL instrument that includes physical and functional domains of QOL and disease symptomatology. The FACT-L is a broader QOL instrument that includes physical, functional, social and emotional domains and disease symptomatology. Both are psychometrically valid and are widely used in the literature, but have not been exclusively evaluated in smokers. Furthermore, there is no ‘gold standard’ instrument since there has never been a correlation study to compare estimates of reliability and validity between these instruments. The purpose of this study is to report the internal consistency and convergence validity of the FACT-L and the LCSS among newly diagnosed lung cancer patients who smoke. This data were collected and analyzed from a larger study examining smoking behavior among newly diagnosed lung cancer patients ( n = 51). Descriptive statistics were calculated on the FACT-L and LCSS scores, internal consistency was assessed by estimating Cronbach's alpha coefficients, and Pearson correlation coefficients were estimated between the two scales. Internal consistency coefficients demonstrated good reliability for both scales, and the two instruments demonstrated a strong correlation, suggesting good convergence validity. Either of these instruments are appropriate measures for QOL in lung cancer patients who smoke. Given the conceptual difference between the two instruments, it is important to carefully consider the research aims when selecting the appropriate QOL measurement instrument.

Tolerability of pemetrexed versus placebo as a maintenance therapy in advanced non-small cell lung cancer: Evidence from a large randomized study

8060 Background: Cytotoxic chemotherapy seeks to reduce or stabilize tumor burden in advanced non-small cell lung cancer (NSCLC). Administration, however, is limited by cumulative toxicity or diminished efficacy over time. We present results on the tolerability of single-agent pemetrexed (Pem) from a phase III, double-blind study, in which maintenance pemetrexed significantly improved progression-free survival (PFS), compared to placebo. Methods: Following 4 cycles of platinum-based doublet chemotherapy, advanced NSCLC patients (pts) with stable or responding disease were randomly assigned 2:1 to receive Pem 500 mg/m2 or placebo infusion every 21 days. Toxicity was assessed using CTCAE (v3) and compared with Fisher’s exact test. Pts completed the Lung Cancer Symptom Scale (LCSS) prior to start of each cycle. Time to worsening of symptoms (TWS) was estimated for each LCSS item based on a 15-point increase from baseline and analyzed using Kaplan-Meier and Cox methods. Results: 663 pts were randomized. Known prognostic factors, as well as baseline LCSS scores, were well balanced between arms. Comparing Pem to placebo: median number (range) of cycles was 4 (1–34) and 3 (1–30); 43% and 25% of pts received ≥ 6 cycles; 4% vs 1% required dose reductions. Deaths on study (any cause) were similar between arms (8.6% vs 9.0%) although pts with ≥ 1 SAE possibly related to study drug were greater for Pem (19 [4.3%] vs 0) Hazard ratios for TWS showed no significant difference or favored Pem. Conclusions: Single-agent Pem is well tolerated as maintenance therapy for pts with advanced NSCLC. Pem provides significantly increased PFS with low rates of toxicity, potential long duration of therapy, and generally comparable-to-placebo patient-reported outcomes. CTCAE Grade 3–4 Toxicities occurring in ≥ 2.5% of Randomized Patients Pem (N=441) Placebo (N=222) P-value Anemia 20 (4.5%) 3 (1.4%) 0.041 Anorexia 11 (2.5%) 2 (0.9%) 0.237 Cough 9 (2.0%) 9 (4.1%) 0.137 Dyspnea 27 (6.1%) 7 (3.2%) 0.135 Fatigue 37 (8.4%) 11 (5.0%) 0.115 Neutropenia 14 (3.2%) 4 (1.8%) 0.448 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company

Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer

This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC). A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days. Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03 (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance. Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.

Overview and Introduction

Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here.After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m2 every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804.Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59–0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34–0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017).Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy.Eli Lilly.

The Relationship Between Cigarette Smoking and Quality of Life After Lung Cancer Diagnosis

To describe the relationship between cigarette smoking and quality of life (QOL) among lung cancer survivors as measured by the lung cancer symptom scale (LCSS). The LCSS was mailed to eligible patients (1,506 patients) between 1999 and 2002. LCSS scores (total and individual QOL components) were compared among different groups of cigarette smokers via univariate independent group testing and multivariate linear models. The modeling process examined group differences adjusted for age, gender, stage, and time of LCSS assessment. LCSS scores were transformed onto a scale of 0 to 100 points in which higher LCSS scores corresponded to a lower QOL. A 10-point difference between groups was defined a priori as being clinically significant. At the time of lung cancer diagnosis, 18% of the patients were never-smokers, 58% were former smokers, and 24% were current smokers. Among survey respondents completing the LCSS at follow-up assessment (1,028 respondents), the mean age was 65.2 years (SD, 10.8 years) and 45% were women. Thirty percent of baseline current smokers continued to smoke at the time of the follow-up assessment (ie, persistent smokers). The adjusted mean total LCSS scores for never-smokers and persistent smokers were 17.6 (SD, 4.02) and 28.7 (SD, 5.09), respectively (p < 0.0001). Seven of the individual LCSS QOL components (ie, appetite, fatigue, cough, shortness of breath, lung cancer symptoms, illness affecting normal activities, and overall QOL) were clinically and statistically (p < 0.001) different between never-smokers and persistent smokers. No clinically significant differences were noted for pain or hemoptysis. Former smokers had intermediate LCSS scores. No dose-response trends were observed between the number of packs of cigarettes smoked per day or the total number of pack-years smoked and the adjusted scores. The hypothesized relationship between smoking status and QOL was supported by this correlational study. Our findings suggest that persistent cigarette smoking after a lung cancer diagnosis negatively impacts QOL scores.

Does second-line therapy for non-small cell lung cancer (NSCLC) result in symptom palliation? Analysis of 484 patients from a randomized trial of pemetrexed vs docetaxel

7035 Background: Second-line treatment for NSCLC patients (pts) with good performance status improves survival. Using the recent trial comparing survival with pemetrexed (500 mg/m2 q3wks) vs docetaxel (75 mg/m2 q3wks) we evaluated the benefit of second-line treatment in terms of palliation, and whether it occurs with less than a major response. Methods: 571 previously treated advanced NSCLC pts, randomized from 3/01 to 2/02, completed the Lung Cancer Symptom Scale (LCSS) which assesses quality of life and 6 symptoms with scores from 0 to 100. Analysis was performed on pts who had data from baseline and ≥1 treatment cycle. Pts were grouped by best overall response: complete or partial, or stable disease (CR/PR/SD) vs progressive disease (PD). A two-factor interaction model with treatment and tumor response as factors was used for analysis. Results: Baseline characteristics were well-balanced between treatment arms with 75% Stage IV and 88% ECOG PS 0/1. Survival time and response rate with pemetrexed were similar to docetaxel (median 8.3 vs 7.9 months [HR 0.99 (95% CI 0.82, 1.20)]; 9.1 vs 8.8%). SD rate was 46% for each arm. 484 pts were included in the LCSS analyses. Baseline LCSS scores were similar between arms. All within-arm improvements were significant except for hemoptysis in docetaxel arm; all between-arm comparisons were not. When pts with CR/PR were divided from those with SD and treatment groups were pooled, mean maximum improvement of Average Symptom Burden Index (average of 6 symptoms) was greater for those CR/PR than those with SD (9.9 vs 4.3); those with PD worsened (-3.7). Conclusions: We conclude that: 1) Symptomatic benefit is achieved in pts with advanced NSCLC receiving second-line single-agent chemotherapy; 2) Pts achieving tumor response or stable disease have a greater likelihood of pt-reported benefit than pts with progressive disease; and 3) Pemetrexed and docetaxel are similarly effective in palliating symptoms. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. AstraZeneca; Eli Lilly & Co. Eli Lilly & Co. Bristol-Myers Squibb; Eli Lilly & Co.

Does cigarette smoking have an impact on quality of life after diagnosis of lung cancer?

INTRODUCTION: Quality of life (QOL) is an important outcome measure for patients with lung cancer. OBJECTIVE: This study assessed the impact of patterns of cigarette use on patientsi QOL as measured with the Lung Cancer Symptom Scale (LCSS). Our hypothesis is that those patients who are current smokers have worse QOL scores than those who never smoked, and former smokers will have scores that are dependent on length of time since smoking abstinence. METHODS: Since January 1, 1997, patients pathologically diagnosed with non-small-cell lung cancer (NSCLC) and patients with small-cell lung cancer (SCLC) were approached to participate in a prospective cohort study. Beginning in 1999, the LCSS has been included in the routine follow-up procedure. A total of 1506 living patients were eligible to complete the LCSS; 1028 patients (68%) who responded to their first follow-up questionnaires, including a QOL assessment, comprise the study population. Additional annual surveys are mailed to the patients. First contacts that included the LCSS were made with the patients at various times from their diagnosis date: 344/1028 (33%), 308/1028 (30%), 254/1028 (25%), and 122/1028 (12%), at 6 months, 1 year, 2 years, and 3 years, respectively. We excluded patients who received their first follow-up at 4 and 5 years due to small numbers. Baseline demographics were summarized utilizing descriptive statistics. To compare the differences in the adjusted LCSS items for the different groups, a multiple logistic regression model was used. The model adjusted the LCSS scores for age, sex, stage, and time of assessment. The total LCSS score and the individual items range from 0 (no symptoms or the best QOL score) up to 100 (maximal amount of symptoms or the worst score); a lo-point difference between groups was considered clinically significant. Two-sided P values of co.05 were considered statistically significant. RESULTS: Responders to the follow-up assessment were more likely to be earlier stage patients and never smokers. Unexpectedly, the nonresponders were younger than responders: 16% of the nonresponders versus 9% of the responders were aged ~50 years at diagnosis. Among the responders who completed the LCSS at the time of first followup assessment (n = 1028), the mean (SD) age was 65.2 (10.7) years, and 45%