Quality-adjusted time without symptoms or toxicity analysis of adjuvant chemotherapy in non-small-cell lung cancer: an analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial.
OBJECTIVE
National Cancer Institute of Canada Clinical Trials Group JBR.10 demonstrated that adjuvant vinorelbine and cisplatin after resection of stage IB-II non-small-cell lung cancer (NSCLC) improved relapse-free and overall survival. However, many patients either are not referred for chemotherapy or decline treatment. To aid in treatment decision making, quality-adjusted survival estimates of the JBR.10 trial were derived using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.


METHODS
Survival curves for treatment (N = 242) and observation groups (N = 240) were partitioned into three health states: time with >or= grade 2 (early or late) chemotherapy-related toxicity (TOX), time in relapse (REL), and time without toxicity or relapse (TWiST). Q-TWiST = u(TOX) x TOX + u(TWiST) x TWIST + u(REL) x REL, where weights u(TOX), u(TWIST), and u(REL) range from 0 to 1. Threshold utility analysis was performed to test the sensitivity of the results to changes in the weights. Weights were derived in an exploratory fashion using different methods. Methods included use of arbitrary values, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) quality-of-life data prospectively collected in JBR.10 (global assessment questions and symptom-based questions), and lastly weights European Quality of Life-Five Dimensions questionnaire collected from early-stage NSCLC (nontrial) patients after resection with discounting for toxicity and relapse. The alpha level was .05.


RESULTS
Threshold utility analysis revealed that adjuvant chemotherapy was preferred for all possible weight values for relapse and toxicity (u(REL), u(TOX)), although the result was not always statistically significant. The adjuvant chemotherapy group had better Q-TWiST in the range of 5 to 6 additional months, which was statistically significant using all methods.


CONCLUSIONS
Adjuvant chemotherapy in early-stage NSCLC improves quality-adjusted survival despite chemotherapy toxicity.
Jang
Raymond W
RW
Department of Medical Oncology, Princess Margaret Hospital/University Health Network, Toronto, Ontario, Canada.
Le Maître
Aurélie
A
Ding
Keyue
K
Winton
Tim
T
Bezjak
Andrea
A
Seymour
Lesley
L
Shepherd
Frances A
FA
Leighl
Natasha B
NB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods; D011446:Prospective Studies; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine