Improving Health-Related Quality of Life in Non–Small-Cell Lung Cancer with Current Treatment Options

doi:10.3816/CLC.2008.n.030

Clinical Lung Cancer

Volume 9, Issue 4, July 2008, Pages 206-212

https://doi.org/10.3816/CLC.2008.n.030 Get rights and content

Abstract

Non–small-cell lung cancer (NSCLC) accounts for > 80% of all lung carcinomas, with the majority of patients presenting with late-stage disease. Selection of an appropriate therapy depends on the stage of disease, with treatment of patients with advanced NSCLC often aimed at palliation of symptoms and improving the well-being of patients. Health-related quality of life (QOL) has been largely ignored as an endpoint in clinical trials for NSCLC, but there is increasing acceptance by clinicians and regulatory authorities that alleviation of symptoms and improved healthrelated QOL should be carefully considered. This article discusses current approaches to measuring health-related QOL. This discussion is followed by a brief review of some of the current treatment options for patients with NSCLC and their effect on health-related QOL.

References (51)

WW Li et al.
Quality of life after lung cancer resection
Thorac Surg Clin
(2004)
D Cella
Quality of life considerations in patients with advanced lung cancer
Semin Oncol
(2004)
TA Plunkett et al.
Quality of life and the treatment of advanced lung cancer
Clin Lung Cancer
(2003)
L Sarna et al.
Assessment of quality of life and symptom improvement in lung cancer clinical trials
Semin Oncol
(2004)
D Cella
The functional assessment of cancer therapy-lung and lung cancer subscale assess quality of life and meaningful symptom improvement in lung cancer
Semin Oncol
(2004)
LJ Fallowfield et al.
Health-related quality of life in patients undergoing drug therapy for advanced non-small-cell lung cancer
Lung Cancer
(2005)
M Helsing et al.
Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group
Eur J Cancer
(1998)
CP Belani et al.
Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer
Ann Oncol
(2005)
R Booton et al.
A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)
Ann Oncol
(2006)
S Thongprasert et al.
Relationship between quality of life and clinical outcomes in advanced non-small cell lung cancer: best supportive care (BSC) versus BSC plus chemotherapy
Lung Cancer
(1999)

I Henoch et al.

The impact of symptoms, coping capacity, and social support on quality of life experience over time in patients with lung cancer

J Pain Symptom Manage

(2007)

EL Smith et al.

Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer

J Pain Symptom Manage

(2001)

ST Lutz et al.

A retrospective quality of life analysis using the Lung Cancer Symptom Scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer

Int J Radiat Oncol Biol Phys

(1997)

JA Langendijk et al.

Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study

Int J Radiat Oncol Biol Phys

(2000)

JL Pujol et al.

Gemcitabine-docetaxel versus cisplatinvinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin

Ann Oncol

(2005)

K Roszkowski et al.

A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC)

Lung Cancer

(2000)

CP Belani et al.

Effect of chemotherapy for advanced non-small cell lung cancer on patients' quality of life. A randomized controlled trial

Lung Cancer

(2006)

J Dancey et al.

Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial

Lung Cancer

(2004)

FA Shepherd et al.

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials

Semin Oncol

(2001)

D Cella et al.

What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) study 5592

J Clin Epidemiol

(2002)

B Movsas et al.

Quality-of-life trials in lung cancer: past achievements and future challenges

Hematol Oncol Clin North Am

(2004)

DT Eton et al.

Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group study 5592

J Clin Oncol

(2003)

D Cella et al.

Clinically meaningful improvement in symptoms and quality of life for patients with non-small-cell lung cancer receiving gefitinib in a randomized controlled trial

J Clin Oncol

(2005)

J Beitz et al.

Quality-of-life end points in cancer clinical trials: the U.S. Food and Drug Administration perspective

J Natl Cancer Inst Monogr

(1996)

JA Sloan et al.

The clinical significance of quality of life assessments in oncology: a summary for clinicians

Support Care Cancer

(2006)

Cited by (27)

The Unique Symptom Burden of Patients Receiving CAR T-Cell Therapy
2021, Seminars in Oncology Nursing
Citation Excerpt :
PRO measures can improve patient-clinician symptom-related communication during active treatment and can improve symptom management and guide treatment decision-making.9 Recognized by regulatory authorities, such as the Food and Drug Administration, valid and reliable PRO measures are acceptable as claim-worthy endpoints in clinical trials.10 Importantly, the content domain for a PRO measure should be derived using direct input from patients who have experienced the disease or treatment in which the measure is intended for use.10
There is little research on the patient experience of symptom burden from CAR T-cell therapy, and no validated measure specific to the symptoms of CAR T-cell therapy currently exists. The purpose of this study was to identify symptoms experienced and to determine the content domain for a patient-reported outcome (PRO) measuring symptom burden for patients who had received standard of care CAR T-cell therapy for advanced B-cell lymphoid malignancies.
Semi-structured qualitative interviews were conducted with a sample of 21 patients who had received CAR T-cell therapy. Content analysis was used to define the symptom burden content domain.
Sixty-two percent of patients were interviewed within 3 months of therapy; 81.0% experienced cytokine release syndrome and 28.6% experienced neurotoxicity. Content analysis found 31 symptoms related to disease and treatment. The most common disease-related symptom identified by patients was pain (43%). The most common symptoms identified by patients as related to CAR T-cell therapy included fatigue (tiredness) (62%), lack of appetite (29%), headache (29%), chills or feeling cold (24%), and feeling confused (24%). The qualitative analysis also confirmed that symptoms interfere with daily activities, work, walking, relationships with others, mood, and enjoyment of life.
Patients who receive standard CAR T-cell therapy experience numerous symptoms related to disease and CAR T-cell therapy, including symptoms related to the T-cell infusion. Symptoms may result in interference with daily activities, relationships, treatment adherence, and mood. Oncology nurses should be aware of and assess symptom related to CAR T-cell therapy.
Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial
2019, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
Experienced daily by our patients with lung cancer, serious impairments and physiological effects, such as nausea, vomiting, cough, shortness of breath, dyspnea, pain, and fatigue, are often combined with prevalent feelings of anxiety, situational depression, and a disruption of familial and social relationships, which have been understudied in the thoracic literature.22,23 The selected survey tools, including LCSS,19 EORTC-QLQ-LC13,17 and FACT-L,18 were among the most common that have been systematically reviewed with investigators' confidence, validated framework, and proper psychometric properties.23 Our trial thus represented one of the early efforts in adopting PRO surveys as parts of endpoints in the new generation of symptom control studies for modern eras in thoracic oncology, although unfortunately it was limited by low patient accrual.
Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis.
We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20 mg of lisinopril or placebo once daily during and up to 3 months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer Therapy–Lung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with χ² and Kruskal-Wallis testing.
Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5 years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, P < .05).
Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety—and possibly beneficial by limited PRO measures—in concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future.
Health-related quality of life in patients with advanced nonsquamous non-small-cell lung cancer receiving bevacizumab or bevacizumab-plus-pemetrexed maintenance therapy in AVAPERL (MO22089)
2013, Journal of Thoracic Oncology
Citation Excerpt :
A real-world study of the importance to patients of symptom palliation—directly assessed via PROs—found that 68% of patients previously treated for advanced NSCLC with first-line platinum-based chemotherapy would choose chemotherapy, even with no survival benefit, over supportive care if it substantially reduced symptoms.35,36 HRQOL for patients with NSCLC treated with maintenance phase bevacizumab or pemetrexed is now being investigated in a number of phase III trials, including AvaALL (MO22097),37 PointBreak,38 and ERACLE.39 In AVAPERL, induction phase therapy was associated with relatively stable functional scores.
In the phase III AVAPERL trial, patients with advanced nonsquamous non–small-cell lung cancer receiving bevacizumab-plus-pemetrexed maintenance after first-line induction had a significant progression-free survival benefit relative to those treated with single-agent bevacizumab maintenance but with an increase in grade ≥3 adverse events. Here, we compare health-related quality of life (HRQOL) between AVAPERL maintenance arms.
Patient-reported outcomes were collected at designated intervals from preinduction to final visits. HRQOL was assessed using the self-administered European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Quality of Life Lung Cancer–Specific Module 13. Differences in scores of 10 points or more between arms were above the minimum important difference threshold and considered clinically meaningful.
During induction, patient-reported coughing symptoms improved slightly, whereas fatigue and appetite loss scores worsened relative to preinduction baseline. During maintenance, changes in mean global health status and the majority of Quality of Life Questionnaire Core 30 and Quality of Life Lung Cancer–Specific Module 13 subscale scores did not differ between trial arms by the minimum important difference defining clinically meaningful (better or worse) patient-reported outcomes. Exceptions were patient-reported role functional status, fatigue symptoms and appetite loss symptoms (favoring bevacizumab), and pain in arm or shoulder symptoms (favoring bevacizumab-plus-pemetrexed maintenance), which differed by clinically meaningful amounts at more than one maintenance assessment.
In AVAPERL, HRQOL remained relatively stable throughout maintenance and was generally similar in both arms. Despite an increase in adverse event rates, the addition of pemetrexed to bevacizumab maintenance resulted in similar stabilization of disease symptoms with improved efficacy outcomes.
Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting: Baseline results of an observational study (FRAME)
2012, Lung Cancer
Citation Excerpt :
At the time of diagnosis, the majority of patients present with advanced (stage IIIB and IV) unresectable NSCLC, which remains incurable. Standard first-line treatments for these patients are platinum-based chemotherapy doublets [2,3], which have been shown to prolong patient survival, relieve symptoms, and improve patients’ quality of life (QoL) [4–6]. A survival benefit has been reported for platinum-based combinations that include the commonly used third-generation cytostatic agents gemcitabine, taxanes (docetaxel, paclitaxel), and vinorelbine [7], and recently for the combination of cisplatin and pemetrexed [8].
FRAME is a prospective observational study of first-line treatments for advanced non-small cell lung cancer (NSCLC). This interim analysis examines the influence of histology and biomarkers on therapeutic decisions. Baseline characteristic, treatment, and diagnostic procedure data were collected on European patients with stage IIIB/IV NSCLC who were treated with any first-line platinum-based doublet, with or without targeted agents, in routine clinical practice. A total of 1567 patients were observed in 11 countries between April 2009 and February 2011. Patients were mostly non-Asian (96.4%), male (71.5%), smokers (84.4%) with stage IV NSCLC (76.6%) and a performance status of 0–1 (82.2%). Median age was 64 years (range, 33–87). First-line treatments were platinum-based combinations with pemetrexed (36.3%), gemcitabine (23.0%), vinorelbine (19.2%), taxanes (18.9%), or other (2.6%), with concurrent targeted agents in 8.4% of patients (mainly bevacizumab, 7.3%). Diagnosis was based on histology in 70.6%, cytology in 20.3%, and both in 9.1% of patients. The final diagnosis was nonsquamous in 72.2% (including ‘not otherwise specified [NOS]’ in 11.0%), squamous in 24.4%, and other in 3.4% of patients, with the most common reasons for NOS diagnosis being ‘subtyping not technically possible’ (42.9%) and ‘not important for treatment decision’ (40.5%). Only 1.1% (6 patients) in the pemetrexed cohort and 0.9% (1 patient) of patients who received bevacizumab had squamous cell carcinoma. At least one immunohistochemical (IHC) marker was used in 53.5% of patients (thyroid transcription factor-1 [TTF-1]: 47.5%, cytokeratin 7 [CK7]: 38.6%, cytokeratin 5/6 [CK5/6]: 17.9%, p63: 8.8%, cluster of differentiation 56 [CD56]: 4.2%, cytokeratin 14 [CK14]: 1.9%, and other: 24.2%). Testing for additional biomarkers was less common, with the most common being for epidermal growth factor receptor (EGFR) mutation status (26.0%). Physician-reported key factors influencing treatment choice were ‘histopathological/cytological diagnosis’ (77.4%), ‘performance status’ (63.2%), and ‘age’ (52.8%). Similar factors were identified using logistic regression models. Frequent histological testing was observed, likely resulting in few NOS diagnoses. In addition, IHC and predictive biomarkers were routinely assessed. Histology, performance status, and age were key factors influencing first-line treatment choice in the routine care of patients with advanced NSCLC.
Clinical Trials. gov registry identifier number: NCT01067794.
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
2012, The Lancet Oncology
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.
Clinical evidence on the undertreatment of older and poor performance patients who have advanced non-small-cell lung cancer: Is there a role for targeted therapy in these cohorts?
2011, Clinical Lung Cancer
A significant proportion of patients who have advanced non–small-cell lung cancer (NSCLC) do not receive treatment even though they may benefit. For instance, studies linking the Surveillance Epidemiology and End Results and Medicare databases show that chemotherapy, even platinum-based doublets, produces a survival benefit in elderly patients who have NSCLC, but only about 30% receive such treatment. Patients with poor performance status and those with significant co-morbidities are also typically undertreated. However, recent clinical evidence suggests that treatment decisions for these populations must be reconsidered. With the emerging availability of validated molecular tools to predict response to specific therapies, the identification of those who may derive substantial benefit from certain interventions is possible even in currently under-served populations. All patients who have advanced NSCLC should be referred for treatment evaluation, even those who are considered ineligible for conventional cytotoxic chemotherapy, and for molecular testing used to match patients with available treatment options.

View all citing articles on Scopus

Electronic forwarding or copying is a violation of US and International Copyright Laws.

Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1525-7304, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.

View full text

Comprehensive ReviewImproving Health-Related Quality of Life in Non–Small-Cell Lung Cancer with Current Treatment Options

Abstract

Thorac Surg Clin

Semin Oncol

Clin Lung Cancer

Semin Oncol

Semin Oncol

Lung Cancer

Eur J Cancer

Ann Oncol

Ann Oncol

Lung Cancer

J Pain Symptom Manage

J Pain Symptom Manage

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Ann Oncol

Lung Cancer

Lung Cancer

Lung Cancer

Semin Oncol

J Clin Epidemiol

Hematol Oncol Clin North Am

Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group study 5592

J Clin Oncol

Clinically meaningful improvement in symptoms and quality of life for patients with non-small-cell lung cancer receiving gefitinib in a randomized controlled trial

J Clin Oncol

Quality-of-life end points in cancer clinical trials: the U.S. Food and Drug Administration perspective

J Natl Cancer Inst Monogr

The clinical significance of quality of life assessments in oncology: a summary for clinicians

Support Care Cancer

Comprehensive Review
Improving Health-Related Quality of Life in Non–Small-Cell Lung Cancer with Current Treatment Options