Quality of life and Q-TWiST were not adversely affected in Ewing sarcoma patients treated with combined anlotinib, irinotecan, and vincristine: (Peking University People's Hospital Ewing sarcoma trial-02, PKUPH-EWS-02)

Sen Dong, Kunkun Sun, Lu Xie, Jie Xu, Xin Sun, Tingting Ren, Yi Huang, Rongli Yang, Xiaodong Tang, Fan Yang, Jin Gu, Wei Guo, Sen Dong, Kunkun Sun, Lu Xie, Jie Xu, Xin Sun, Tingting Ren, Yi Huang, Rongli Yang, Xiaodong Tang, Fan Yang, Jin Gu, Wei Guo

Abstract

Background: Combined treatment with anlotinib, irinotecan, as well as vincristine for advanced Ewing sarcoma (EWS) has been verified been effective in the prospective trial of Peking University People's Hospital EWS trial-02. We aimed to assess the dynamic changes in health-related quality of life (QoL) and the benefit-risk in quality-adjusted survival in current study.

Methods: Twelve "pediatric" patients and 23 "adult" patients were enrolled. QoL was assessed with the EORTC QLQ-C30 for adults and PedsQL 3.0 Cancer Module for children and adolescents. The quality-adjusted time without symptoms of disease progression or toxicity of treatment (Q-TWiST) analysis was used to describe treatment results.

Results: Progression-free survival was not accompanied by diminished QoL. Differences in scores on the QoL global health status and specific functioning before, during, and after treatment were not significantly different with time (P = .14 for adults and .91 for children). During treatment, there was a statistically insignificant trend towards improved QoL with reduced tumor burden (P = .14 for adults and .10 for children), but QoL significantly declined with progression of disease (P = .05 for adults and .04 for children). The most common adverse events were neutropenia (12.1%), leukopenia (16.6%), anemia (12.7%), and diarrhea (4.93%). Results across the trial analyses showed that the median time of Q-TWiST was 0.73 (interquartile range, 0-1.57) months, whereas the median time with toxicity before disease progression was 3.9 (interquartile range, 2.3, 6.1).

Conclusion: QoL exhibited a trend towards improvement in accordance with high objective response in this trial with the receipt of combination therapy of anlotinib, vinsristine, and irinotecan for advanced EWS. The toxicity profile did not translate into significantly worse overall scores during treatment.

Trial registration: ClinicalTrials.gov NCT03416517.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1
Figure 1
Dynamic changes of adults’ GHS scores according to EORTC QLQ-C30 over time. EORTC QLQ-C30 = 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire, GHS = global health status.
Figure 2
Figure 2
Dynamic changes of children's general scores (GHS) according to PedsQL3.0 Generic Core Scales over time. GHS = global health status.
Figure 3
Figure 3
Dynamic changes of adults’ functioning scales for adults according to EORTC QLQ-C30 over time, which included physical, role, emotional, cognitive, and social functioning. EORTC QLQ-C30 = 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire, OS = overall survival, PFS = progression-free survival, REL = relapse, TOX = toxicity, TWiST = time without symptoms or toxicities.
Figure 4
Figure 4
Dynamic changes of children's scale descriptives of QoL according to EORTC QLQ-C30 over time, which included pain and hurt (2 items), nausea (5 items), procedural anxiety (3 items), treatment anxiety (3 items), worry (3 items), cognitive problems (5 items), perceived physical appearance (3 items), and communication (3 items). EORTC QLQ-C30 = 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire, QoL = quality of life.
Figure 5
Figure 5
All patients’ Q-TWiST over time. Crosses indicate censoring. (1) EWiST: time from starting treatment to disease progression without ≥grade 3 AEs, which was defined as PFS time minus time with TOX; (2) TOX: time with ≥grade 3 AEs after starting treatment and before disease progression; (3) REL: time from disease progression to death, which was defined as OS minus PFS time. AEs = adverse events, PFS = progression-free survival, OS = overall survival, Q-TWiST = Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment, REL = relapse, TOX = toxicity, TWiST = time without symptoms or toxicities.

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