The impact of second-line agents on patients' health-related quality of life in the treatment for non-small cell lung cancer: a systematic review.
OBJECTIVE
In advanced non-small cell lung cancer (NSCLC), progressive disease burdens patients considerably. Second-line (2L) chemotherapy improves survival marginally but humanistic outcomes (i.e., quality of life, QOL) are underreported. The impact of 2L therapy remains an important consideration for patients and caregivers, and there have been QOL reviews for 1L, but not 2L, therapies. This review assessed QOL outcomes of approved, guideline-supported 2L chemotherapy with docetaxel, erlotinib, gefitinib, and pemetrexed in advanced NSCLC.


METHODS
Clinical trial reports of approved, guideline-supported 2L or maintenance therapy for NSCLC published from 2000 to 2010 were identified from PubMed/Medline and clinical meetings. Outcomes were stratified by overall QOL impact, domain/symptom-specific effects, effect over time, and subgroup effects.


RESULTS
Of 145 studies identified, 24 full-text articles were retained. Studies with docetaxel versus best supportive care (n = 1) and active comparators (n = 4) reported non-significant overall QOL improvements, as did studies of gefitinib versus placebo and active comparator (n = 7). Overall QOL improvements were seen for gefitinib versus docetaxel (n = 2) and gefitinib in a single-arm study (n = 1). At the symptom level, studies of docetaxel (n = 4/7), gefitinib (n = 7/9), and pemetrexed (n = 1) reported non-significant results. Subgroup analyses indicated improved QOL outcomes for gefitinib-treated responders versus non-responders, worse QOL for gefitinib-treated smokers versus placebo, worse QOL for gefitinib-treated Asian patients versus placebo, and longer time to symptom deterioration in erlotinib versus placebo-treated elderly patients.


CONCLUSIONS
Significant improvements in overall QOL with 2L chemotherapy for advanced NSCLC were infrequent. Single-arm studies and those with less toxic regimens more commonly provided statistically significant improvements in QOL outcomes. Methodological heterogeneity impedes cross-study QOL comparisons.
Abbott Laboratories, 200 Abbott Park Road, GMH1, AP30-3NW, Abbott Park, IL 60064, USA.
Arijit
A
Ganguli
Phillip
P
Wiegand
Xin
X
Gao
John A
JA
Carter
Marc F
MF
Botteman
Saurabh
S
Ray
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006304:Health Status; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D018434:Sickness Impact Profile; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib