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

Abstract

Purpose: 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.

Conclusion: Adjuvant chemotherapy in early-stage NSCLC improves quality-adjusted survival despite chemotherapy toxicity.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Partitioned survival curves for (A) the observation group and (B) the vinorelbine and cisplatin group. REL, relapse; TOX, toxicity; TWiST, time without symptoms or toxicity; OS, overall survival; DFS, disease-free survival.

Fig 2.

Threshold utility analysis with a 95% CI and contour lines. The diagonal contour lines indicate the units of months gained in quality-adjusted time without symptoms or toxicity (Q-TWiST) for different weights of toxicity (TOX) and relapse (REL). The weight for TWiST is defined as uTWIST = 1. The gold area represents weights for which the improvement in Q-TWiST for vinorelbine and cisplatin is not statistically significant. The blue area represents weights for which the improvement in Q-TWiST for vinorelbine and cisplatin is statistically significant.

Fig A1.

Quality-adjusted time without symptoms or toxicity (QTWiST) gain function with method 4: European Quality of Life–Five Dimensions Index Score. The solid line gives the average months of Q-TWIST gained for the vinorelbine and cisplatin group compared with the observation group as a function of years from random assignment. The blue region shows the ranges for the Q-TWiST gain function as the weight coefficients vary between 0 and 1.