Lung Cancer-specific Module Research Articles

The patient outcomes with EGFR-mutated advanced non-small-cell lung cancer receiving aumolertinib as first-line treatment.

e20619 Background: As a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib demonstrated superior progression-free survival and a well-tolerated toxicity profile to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, the real-world impact of aumolertinib in the first-line treatment on patients' HRQoL still remains unclear. Methods: Advanced NSCLC patients with sensitizing EGFR mutations treated with aumolertinib 110 mg daily in the first-line treatment were prospectively enrolled and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and EORTC Quality of Life lung cancer-specific module (QLQ-LC13) information were collected. Efficacy evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was also recorded here. Prespecified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling hands or feet, chest pain, arm or shoulder pain and pain of other sites. Results: Totally, 33 patients in the first-line treatment were included and 23 patients had efficacy information up to Jan 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate (ORR) and disease control rate (DCR) was 65.2% and 91.3%, respectively. All the patients haven’t reached the time to deterioration and the progression free survival(PFS) and overall survival is not reach. EORTC QLQ-LC30 showed general health status scale and functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by EORTC QLQ-LC13 showed cough, sore mouth or tongue, chest pain, arm or shoulder pain and pain of other sites, were improved significantly after aumolertinib treatment (P < 0.05). Conclusions: General health status, functional status and key symptoms improved from baseline in patients with advanced NSCLC receiving aumolertinib as first-line treatment. The ORR and DCR in our study was comparable in those showed the AENEAS trial.

Efficacy of acupuncture for a cough-related symptom cluster in patients with lung cancer: A randomized controlled trial

PurposeThis study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients. MethodsBetween December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons. ResultsCompared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = −0.32, 95% CI, −0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = −0.11, 95% CI, −0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = −0.05, 95% CI, −0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = −0.66, 95% CI, −0.99 to 0.33, P < 0.001) post-intervention. ConclusionsAcupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath.

Change in Quality of Life after Stereotactic Body Radiation Therapy (SBRT) on a Prospective Trial of Peripheral Stage I or II Non-Small Cell Lung Cancer Predicts Survival

We previously reported the results of a randomized, multi-institutional phase II clinical trial evaluating one versus three fractions of SBRT for peripheral Stage I to II non-small cell lung cancer (NSCLC). A secondary objective to compare quality of life (QOL) data and its association with survival outcomes is reported. Medically inoperable patients with biopsy-proven peripheral T1-2N0M0 NSCLC were enrolled. Patients were randomized to 30 Gy in 1 fraction (arm 1) or 60 Gy in 3 fractions (arm 2) and stratified by performance status. QOL scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC QLQ Lung Cancer-Specific Module (EORTC QLQ-LC13) questionnaires were required at baseline and each follow-up visit. Univariate models were generated to evaluate associations between QOL scores and survival with 95% confidence intervals (CI) calculated at each time point. Among 98 patients enrolled (49 in each arm), 88 patients had data available for QOL analysis. At 6 month follow up, patients with stable or decreased (n = 49) versus those with increased global QOL scores (n = 27) had worse progression-free survival (HR [Hazards' Ratio] 2.32 [CI, 1.14-4.73], p = 0.021) and overall survival (HR 2.13 [CI, 1.01-4.51], p = 0.048). Similar results persisted at the 12 month follow up for progression-free survival (HR 3.90 [CI, 1.52-10.04], p = 0.016) and overall survival (HR 3.25 [CI, 1.25-8.43], p = 0.016). Median overall survival for patients with stable or decreased global QOL versus increased global QOL at 6 month follow up was 39.0 vs 60.3 months (p = 0.032). Change in QOL is an early predictor of survival following SBRT for patients with peripheral early-stage NSCLC.

Patient-reported Physical Function Is Associated With Survival After Lung Resection for Non-Small Cell Lung Cancer

BackgroundWe investigated the association between preoperative quality of life and long-term survival in patients undergoing surgical resection for non-small cell lung cancer. MethodsRetrospective analysis was conducted on 388 consecutive patients who completed the quality of life assessment through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and lung cancer specific module (LC13), before anatomic lung resection for non-small cell lung cancer (2014-2018). Survival distribution was estimated by the Kaplan-Meier method. Cox proportional hazards regression and competing risk regression analyses were used to assess the independent association of preoperative patient-reported outcomes with overall and cancer-specific survival. ResultsHigher score in patient-reported physical functioning was significantly associated with longer overall survival. Factors significantly associated with poorer overall survival remained older age (P = .005), low body mass index (P = .007), male sex (P < .001), and nodal involvement (P = .007). Competing regression analysis found that worse baseline lung cancer-specific dyspnea (P = .03), low body mass index (P = .01), worse performance status (P = .03), and lymph node involvement (P = .01) were significantly associated with poorer cancer-specific survival. ConclusionsHigher patient-reported physical function score was associated with longer overall survival after resection. Our study highlights the significance of routinely collecting quality of life data to aid preoperative decision making in non-small cell lung cancer.

Clinical Efficacy of Thoracoscopic Surgery with the da Vinci Surgical System versus Video-Assisted Thoracoscopic Surgery for Lung Cancer

Objective To assess the clinical efficacy of thoracoscopic surgery with the da Vinci surgical system versus video-assisted thoracoscopic surgery (VATS) for lung cancer. Methods From August 2019 to December 2020, 193 patients with lung cancer assessed for eligibility scheduled for surgery in our hospital were recruited and assigned at a ratio of 1 : 1 to receive VATS (control group) or thoracoscopic surgery with the da Vinci surgical system (research group). The primary measurement is the clinical efficacy of the two surgical modalities. Results The baseline features of the research group were comparable with those of the control group (P > 0.05). Besides, the two groups showed similar tumor types, tumor locations, and clinicopathological staging (P > 0.05). Da Vinci surgical system-assisted thoracoscopic surgery had short operative time, less intraoperative blood loss, better lymph node dissection, and lower intraoperative conversion rates compared to VATS. Compared with the control group, the research group had significantly higher postoperative forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), the functional assessment of cancer therapy-general module (FACT-G) of the FACT-lung (FACT-L) Chinese version V4.0, lung cancer-specific module scores, and total scores (P < 0.05). The research group showed better postoperative drainage volume, shorter intubation duration, and length of hospital stay and a lower incidence of complications versus the control group (P < 0.05). The da Vinci surgical system reduced the probability of intraoperative mistakes and better ensured a safe and satisfactory surgery. Conclusion The thoracoscopic surgery with the da Vinci surgical system better reduces intraoperative and postoperative bleeding, shortens drainage and intubation duration, enhances the lung function and survival quality of patients, and lowers the risk of surgical mistakes to ensure surgical safety versus VATS.

An Investigation of Symptom Clusters and Sentinel Symptoms During the First 2 Cycles of Postoperative Chemotherapy in Patients With Lung Cancer.

Lung cancer has the highest incidence and mortality of all cancers in China. Patients after a lobectomy experience serious physical and psychological symptoms during chemotherapy. Studies are lacking about symptom clusters (SCs) and sentinel symptoms during the postoperative chemotherapy period in lung cancer patients. The aim of this study was to explore SCs and sentinel symptoms during cycles 1 and 2 of postoperative chemotherapy in patients with lung cancer. Using a longitudinal study design, patients in treatment for lung cancer were measured at 2 separate points following a lobectomy: chemotherapy cycle 1 and chemotherapy cycle 2. The MD Anderson Symptom Inventory lung cancer-specific module and First Appearance of Symptoms Time Sheet were completed. A total of 180 postoperative patients with lung cancer participated in the study. Four SCs were identified at chemotherapy cycle 1: gastrointestinal SC, respiratory tract SC, psychological SC, and somatic SC. The sentinel symptoms were nausea, cough, sadness, and fatigue. At chemotherapy cycle 2, similar SCs were identified, with the exception of merging the psychological SC and somatic SC, resulting in 3 clusters: gastrointestinal SC, respiratory tract SC, and psychological-somatic SC. The sentinel symptoms were nausea, cough, and fatigue. Symptom clusters and sentinel symptoms were stable during the first 2 cycles of postoperative chemotherapy in patients with lung cancer. The understanding of SCs and sentinel symptoms could be beneficial to assess and manage both in postoperative patients with lung cancer during chemotherapy. Nurses should pay close attention to sentinel symptoms and develop effective interventions.

Patient-reported symptoms, functioning, and quality of life (QoL) in patients treated with cemiplimab monotherapy for first-line treatment of advanced NSCLC with PD-L1 ≥ 50%: Results from EMPOWER-Lung 1 study.

9078 Background: Cemiplimab, a PD-1 inhibitor, improved survival and progression-free survival vs platinum doublet chemotherapy (chemo) in patients (pts) with advanced NSCLC and PD-ligand(L)1 expression ≥50% in the EMPOWER-Lung 1 Phase 3 study (NCT03088540). Since pts with advanced NSCLC have a high symptom burden that adversely impacts QoL and functioning, these outcomes were evaluated as secondary endpoints in the clinical trial. Methods: Pts with advanced NSCLC with PD-L1 expression ≥50% and ECOG performance status ≤1 were randomized to IV cemiplimab 350 mg Q3W (n=356) or platinum doublet chemo (n=354). At baseline (BL) and day 1 of each treatment cycle (C) to C15, pts were administered the EORTC core questionnaire (QLQ-C30) and its lung cancer specific module (QLQ-LC13) to assess symptoms, functioning, and Global Health Status (GHS)/QoL. In the intent-to-treat population, mixed-effects repeated measures models were used to estimate least squares (LS) mean change from BL on all scales. Kaplan–Meier analysis estimated time to definitive deterioration, defined as worsening ≥10 points from BL observed at all subsequent time points or patient withdrawal after worsening; hazard ratios (HR) with 95% CIs estimated the likelihood of definitive deterioration. Results: BL scores showed moderate to high levels of functioning and low symptom burden. Cemiplimab-treated pts had lower likelihood of definitive deterioration vs chemo on key symptoms of dyspnea, cough, pain in chest, pain in other body parts, fatigue, nausea/vomiting, appetite loss, constipation, and diarrhea vs chemo (all P&lt;.05). Treatment-related symptoms of peripheral neuropathy and alopecia had a lower likelihood of definitive deterioration with cemiplimab vs chemo (both P&lt;.05). Cemiplimab resulted in significantly greater improvements vs chemo on all functioning scales and reduced the likelihood of definitive deterioration as indicated by HR &lt;1 (Table). GHS/QoL improvements with cemiplimab at C2 were maintained to C15; LS mean change (SE) from BL across all timepoints was 7.1 (1.0) for cemiplimab vs 1.7 (1.2) for chemo ( P&lt;.0001). Conclusions: In pts with advanced NSCLC and PD-L1 expression ≥50%, cemiplimab significantly improved GHS/QoL, functioning, and most symptoms vs chemo. Over 1 year of treatment, cemiplimab delayed worsening of key lung cancer symptoms and functioning. Clinical trial information: NCT03088540. [Table: see text]

Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor–naive ALK + non−small cell lung cancer (ALTA-1L)

ObjectiveIn ALTA-1 L, first-line brigatinib versus crizotinib significantly prolonged progression-free survival in advanced ALK-positive (ALK+) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQOL) outcomes from ALTA-1 L. Materials and MethodsHRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) and lung cancer–specific module (QLQ-LC13). HRQOL time to worsening, change from baseline, and duration of improvement were analyzed. ResultsEORTC QLQ-C30 and QLQ-LC13 compliance was >90 % for both groups (n = 131 each). Brigatinib versus crizotinib significantly delayed time to worsening in the EORTC QLQ-C30 global health status (GHS)/QOL (median: 26.74 vs 8.31 months; hazard ratio [HR]: 0.70; 95 % CI: 0.49, 1.00; log-rank P = 0.0485); emotional functioning, social functioning, fatigue, nausea and vomiting, appetite loss, and constipation scales (log-rank P < 0.05); delays in time to worsening for the physical, role, and cognitive functioning scales were not statistically significant. Mean change from baseline showed greater improvement in GHS/QOL and most EORTC QLQ-C30 functional and symptom scales with brigatinib versus crizotinib. Among patients with GHS/QOL improvement, brigatinib had longer duration of improvement versus crizotinib (median: not reached vs 11.99 months); similar results were seen in the physical, role, emotional, and social functioning; fatigue; nausea and vomiting; and appetite loss scales. Median time to worsening in dyspnea (QLQ-LC13) was 23.98 versus 8.25 months (brigatinib vs crizotinib; HR: 0.64; 95 % CI: 0.39, 1.05). ConclusionBrigatinib significantly delayed time to worsening and prolonged duration of improvement in GHS/QOL versus crizotinib, supported by improvement in functional and symptom scores. These preliminary analyses suggest brigatinib is the first ALK inhibitor with better HRQOL versus another ALK inhibitor in ALK inhibitor–naive advanced ALK + NSCLC.

Gender effects on quality of life and symptom burden in patients with lung cancer: results from a prospective, cross-cultural, multi-center study.

BackgroundLung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module.MethodsIn a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn.ResultsA total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points).ConclusionsThis study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.

EP1.01-75 Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Most Appropriate Fractionation?

Radiotherapy is the one of the most effective modalities to palliate the symptoms (hemoptysis, pain, breathlessness) of poor-prognosis patients with advanced non-small-cell lung cancer. Most appropriate dose schedule however remains debatable. We conducted a retrospective analysis that compared the efficacy of radiotherapy schedules consisting of 5 fractions of 4 Gy (5 x 4 Gy) versus 10 fractions of 3Gy (10 x 3 Gy) in advanced Non Small Cell Lung Cancer (NSCLC). The end point evaluated was symptomatic relief. Between July 2016 and September 2017, 60 patients with advanced NSCLC were randomised to either 5 fractions of 4 Gy (5 x 4 Gy): Arm A or 10 fractions of 3Gy (10 x 3 Gy):Arm B. The eligibility criteria was histologically or cytologically confirmed NSCLC, age ≥ 30, stage III or IV disease, Karnofsky performance status (PS) ≥ 40, expected survival ≥ 3 months. The quality-of-life was assessed using the patient records: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer–specific module QLQ-LC13. The primary study end points was control of symptoms viz cough, hemoptysis, pain and dyspnea, and the secondary end point was to evaluate Overall Survival (OS). 52 out of 60 patients were males,18/60 had lost to follow up. Majority of patients presented in 5th and 6th decade of their lives, mean age of presentation was 58.87 (Range31-80). Majority (69%) of patients had presented with poor KPS 70 or less. Most common presenting symptom was cough with expectoration (74.66%) followed by hemoptysis (47.33%). Post treatment 36% reported reduced cough, 44% reported reduced dyspnea, 57% reported reduced pain and 90% reported reduced hemoptysis within 20 weeks from start of treatment, with no statistical difference among the groups. Except for improved hemoptysis at week 5 in Arm A (P =0.03), there was no difference among the groups. Furthermore, the palliative effect of symptoms seemed to last throughout the planned follow-up period. Overall survival for all patients (n=42) revealed no significant survival difference among the treatment groups (P = 0.2). The median survival was 6.2 and 6.7 months in arm A and B, respectively. Hypofractionated regimen of 20Gy/5 fractions is atleast as effective at providing symptomatic relief and yields equivalent survival as 30Gy/10 fractions in patients with advanced non-small cell lung cancer and thoracic symptoms besides having the advantage of fewer visits to hospital as well.

Traditional Korean Medicine for Non-Small Cell Lung Cancer Patient Undergoing Pembrolizumab Immunotherapy: A Case Report

Objective: The purpose of this study was to report the effect of traditional Korean medicine (TKM) in alleviating the side effects of lung cancer patient undergoing immunotherapy. Method: A 43-year-old man, who was diagnosed with non-small cell lung cancer, received pembrolizumab treatments. The patient was treated with acupuncture and herbal medicine (Geoeoyangpye-tang) to control various uncomfortable symptoms. The degree of pain was measured by the numeric rating scale (NRS). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13 questionnaire) were used to assess the change in the quality of life. Results: After the TKM treatment, the flank pain and arthralgia based on the NRS were significantly improved. Various uncomfortable symptoms such as fatigue, dyspnea, insomnia, and loss of appetite were also significantly improved, based on the EORTC QLQ-C30 and EORTC QLQ-LC13. The size of the primary tumor was decreased during treatment. The disease status was stable radiologically after two months from discharge. Keywords: non-small cell lung carcinoma, immune checkpoint inhibitor, PD-1 inhibitor, pembrolizumab, traditional Korean medicine, case report

Perioperative course and quality of life in a prospective randomized multicenter phase III trial, comparing standard lobectomy versus anatomical segmentectomy in patients with non-small cell lung cancer up to 2 cm, stage IA (7th edition of TNM staging system)

ObjectivesFor early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available. Materials and methodsWe conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery. Results108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (p = 0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (p = 0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (p < 0.001) and cognitive functioning (p = 0.025), dyspnea (p < 0.001) and fatigue (p = 0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (p = 0.016 after 12 months). ConclusionIn patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.

Quality of life results from a randomized, double-blinded, placebo-controlled, multi-center phase III trial of anlotinib in patients with advanced non-small cell lung cancer

ObjectivesAnlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret. In the phase III ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small-cell lung cancer (NSCLC) patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study assessed quality of life (QoL) in these patients. MethodsPatients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. The QoL were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the associated EORTC Quality of Life Lung Cancer Specific Module (QLQ-LC13) at baseline, end of cycle 1, end of every two cycles, and at the final visit. The analyses were conducted in the first 6 cycles. Differences in scores of 10 points or more between two arms or from baseline were considered clinically meaningful. ResultsA total of 437 patients were assigned to anlotinib (n = 294) and placebo (n = 143). The completion rates of the QoL questionnaires were from 69.9% to 97.0%. Mean scores of QLQ-C30 and QLQ-LC13 subscales were similar in the anlotinib and placebo arms at baseline. Compared to placebo, anlotinib improved role functioning, social functioning, dyspnea, insomnia, constipation and financial problems. Only sore mouth or tongue symptom was worse in the anlotinib arm than in the placebo arm. ConclusionsAnlotinib improved quality of life versus placebo in advanced NSCLC patients who had received at least two previous chemotherapies. The QoL analyses provided evidence that anlotinib should be a choice for the third-line treatment or beyond in advanced NSCLC.

Development of a hospital-based patient-reported outcome framework for lung cancer patients: a study protocol

BackgroundPatient-reported outcome (PRO) data is central to the delivery of quality health care. Establishing sustainable, reliable and cost-efficient methods for routine collection and integration of PRO data into health information systems is challenging. This protocol paper describes the design and structure of a study to develop and pilot test a PRO framework to systematically and longitudinally collect PRO data from a cohort of lung cancer patients at a comprehensive cancer centre in Australia.MethodsBest-practice guidelines for developing registries aimed at collecting PROs informed the development of this PRO framework. Framework components included: achieving consensus on determining the purpose of the framework, the PRO measures to be included, the data collection time points and collection methods (electronic and paper), establishing processes to safeguard the quality of the data collected and to link the PRO framework to an existing hospital-based lung cancer clinical registry. Lung cancer patients will be invited to give feedback on the PRO measures (PROMs) chosen and the data collection time points and methods. Implementation of the framework will be piloted for 12 months. Then a mixed-methods approach used to explore patient and multidisciplinary perspectives on the feasibility of implementing the framework and linking it to the lung cancer clinical registry, its clinical utility, perceptions of data collection burden, and preliminary assessment of resource costs to integrate, implement and sustain the PRO framework. The PRO data set will include: a quality of life questionnaire (EORTC-QLQ-C30) and the EORTC lung cancer specific module (QLQC-LC-13). These will be collected pre-treatment (baseline), 2, 6 and 12 months post-baseline. Also, four social isolation questions (PROMIS) will be collected at baseline.DiscussionIdentifying and deciding on the overall purpose, clinical utility of data and which PROs to collect from patients requires careful consideration. Our study will explore how PRO data collection processes that link to a clinical data set can be developed and integrated; how PRO systems that are easy for patients to complete and professionals to use in practice can be achieved, and will provide indicative costs of developing and integrating a longitudinal PRO framework into routine hospital data collection systems.Trial registrationThis study is not a clinical trial and is therefore not registered in any trial registry. However, it has received human research ethics approval (LNR/16/PMCC/45).

Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6)

IntroductionIn LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported.Patients and MethodsLung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory.ResultsCompared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations.ConclusionsThese exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups.Electronic supplementary materialThe online version of this article (10.1007/s40271-017-0287-z) contains supplementary material, which is available to authorized users.

Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy

IntroductionIn the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. Patients and MethodsPatients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL. ResultsQuestionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL. ConclusionIn patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib.

The Humanistic Burden of Small Cell Lung Cancer (SCLC): A Systematic Review of Health-Related Quality of Life (HRQoL) Literature.

Background: Little is known about the humanistic burden of small cell lung cancer (SCLC), specifically the impact on health-related quality of life (HRQoL). The aim of this systematic literature review was to explore the impact of SCLC on HRQoL and the patient reported outcomes (PROs) used to capture this impact.Methods: We conducted a systematic search of Medline®, Embase, and PsycINFO, oncology organization websites and conference proceedings within the past 10 years. Articles reporting HRQoL outcomes of SCLC patients were selected.Results: Twenty-seven eligible publications were identified. Global or overall impact on HRQoL (n = 21) was reported most often, with considerably fewer reporting individual domains that comprise HRQoL. Results indicated that HRQoL was negatively impacted in SCLC patients in comparison to the normal population in most domains. Overall, the domains measuring physical functioning and activities of daily living were most impacted. However, results on cognitive and emotional functioning were inconclusive. The impact on HRQoL may be least in both limited disease and extensive disease (ED) SCLC patients who have responded to treatment, and greatest in ED patients who were treatment naïve. The most frequently used PROs were the EORTC QLQ-C30 core cancer instruments, the lung cancer specific module the EORTC QLQ-LC13, LCSS, and EQ-5D.Conclusion: There exists a paucity of reporting on SCLC HRQoL outcomes. This extends to the reporting of domain level scores and by patient sub-group. Greater reporting at a granular level is recommended to allow for more robust conclusions to be made.

Reference Data for Standardized Quality of Life Questionnaires in Indian Patients with Brain Metastases from Non-small Cell Lung Cancer: Results from a Prospective Study.

IntroductionReference data for European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires do not include studies from the Indian subcontinent. The objective of the current study was to establish a reference dataset for Indian patients of non-small cell lung cancer (NSCLC) presenting with brain metastases (BM).Material and methodsOne hundred forty patients with NSCLC with BM treated between 2012-2015 were registered in a prospective cohort study (CTRI/2013/01/003299). The baseline quality of life was evaluated using the EORTC general quality of life questionnaire QLQ-C30 and lung cancer specific module LC13. Minimum important difference (MID) scores for individual domains of the EORTC QLQ-C30 and LC13 questionnaires were derived (MID = 0.2 x standard deviation) from the reference data for patients with recurrent/metastatic lung cancers. In addition, a systematic review was conducted to identify studies reporting baseline quality of life scores for recurrent/metastatic NSCLC.ResultsScores of several functional as well as symptom scales in the current NSCLC population differed by more than the MID from the baseline mean scores in the reference EORTC population as well as that reported from other studies. Differences in mean score from the EORTC reference data ranged from 6.2 and 9.4 points for the role functioning and cognitive functioning domains. In the symptom scales, the largest differences were observed for the financial difficulties (23.9) scores for the QLQ-C30 and peripheral neuropathy (21.7) for LC13 questionnaires.ConclusionThe current study demonstrates that baseline reference scores need to be established for patients from the Indian subcontinent. The findings from the current study have important implications for studies employing quality of life (QOL) assessment in the Indian NSCLC patient population.

P3.02a-012 Patient-Reported Symptoms and Quality of Life (QoL) in East Asian Patients with ALK+ NSCLC Treated with Crizotinib vs Chemotherapy: Topic: ALK Clinical

The phase 3 study PROFILE 1014 showed a superior outcome of crizotinib over pemetrexed-cisplatin/carboplatin (PCC) in ALK+ NSCLC.1 PROFILE 1029 is an ongoing phase 3 study of similar design (NCT01639001) conducted in an East Asian population in China, Hong Kong, Malaysia, Taiwan, and Thailand. Here, we present findings on patient-reported symptoms and QoL. Patients with previously untreated, ALK+ advanced NSCLC were randomized 1:1 (stratification: ECOG PS 0 or 1 vs 2) to crizotinib 250 mg PO BID or pemetrexed 500 mg/m2 with cisplatin 75 mg/m2 or carboplatin to an AUC of 5–6 mg·min/mL, IV Q3W for ≤6 cycles. The EORTC QLQ-C30 and lung cancer-specific module (QLQ-LC13) questionnaires were completed at baseline, days 1, 7, and 15 of Cycle 1, day 1 of each subsequent cycle, and at end-of-treatment or withdrawal. Mixed model analyses were used to evaluate changes from baseline and between treatment arms. Patients, who received crizotinib (n=103) had significantly longer median time to deterioration (TTD) for chest pain, dyspnea, or cough compared to PCC (n=98) (2.8 mo [95% CI: 1.4, 6.9] vs 0.3 mo [95% CI: 0.3, 0.5], respectively; HR=0.432 [95% CI: 0.307, 0.610]; P<0.0001). Crizotinib treatment, compared to PCC, was associated with a significantly greater change from baseline in global QoL and physical, role, cognitive, and social functioning (Table). QLQ-C30 results demonstrated that crizotinib-treated patients experienced either improvement or reduced worsening of most symptoms compared to PCC-treated patients. QLQ-LC13 data showed improvement or reduced worsening across all symptoms for crizotinib, relative to PCC. Crizotinib treatment significantly delayed TTD of lung cancer symptoms (chest pain, cough, dyspnea). Crizotinib was associated with significantly greater improvements from baseline in key patient-reported lung cancer symptoms and global QoL, compared with PCC.

Symptom and Quality of Life Improvement in LUX-Lung 6: An Open-Label Phase III Study of Afatinib Versus Cisplatin/Gemcitabine in Asian Patients With EGFR Mutation-Positive Advanced Non–small-cell Lung Cancer

In the phase III, LUX-Lung 6 trial, afatinib prolonged progression-free survival (PFS) versus cisplatin/gemcitabine in Asian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). This article provides detailed assessments of patient-reported outcomes (PROs), a LUX-Lung 6 secondary end point, and explores the relationship between PFS and health-related quality of life (QoL) in these patients. Patients (n = 364) were randomized (2:1) to oral afatinib (40 mg/day) or up to six cycles of cisplatin/gemcitabine (21-day cycle; cisplatin 75 mg/m(2) [d1]; gemcitabine 1000 mg/m(2) [d1,8]). QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its lung cancer-specific module. The relationship between PFS (investigator assessment and independent review) and QoL was evaluated using analysis of covariance and a longitudinal model. More patients treated with afatinib versus cisplatin/gemcitabine showed improvements in global health status/QoL (p < 0.0001) and physical (p < 0.0001), role (p = 0.013), and social (p < 0.001) functioning scales. Delayed symptom deterioration and better QoL over time was also observed with afatinib. QoL measured before tumor assessment was considerably poorer for patients with progression than those without progression, with significant differences in mean scores at multiple assessment time points. Results from the longitudinal analysis consistently demonstrated a significant negative impact of progression on QoL (p < 0.0001). Afatinib improved PFS and PROs versus chemotherapy in EGFR mutation-positive NSCLC patients. Progression was associated with statistically significant worsening in QoL measured before tumor assessment, underscoring the value of PFS as a clinically relevant end point.