Underreporting of health-related quality of life in trials of matched targeted therapies for advanced or metastatic cancer.

Abstract

e23188 Underreporting of Health-Related Quality of Life in Trials of Matched Targeted Therapies for Advanced or Metastatic Cancer Background: In people with advanced cancers, genotype-based matched targeted therapies (MTTs) have demonstrated a clinically significant survival benefit in the first-line setting. However, there is inconsistent evidence of survival benefit with MTTs in people with heavily pretreated cancers. For these individuals, improving health-related quality of life (HRQoL) is increasingly becoming an important goal of treatment. We conducted a systematic review to assess the reporting and compliance of HRQoL in trials evaluating genotype-based MTTs in this population. Methods: We searched medical databases (e.g., Medline, Embase) and trial registries for eligible randomized controlled trials (RCTs) involving participants with advanced solid or haematological malignancies who had progressed after at least one line of systemic therapy and subsequently received MTTs. Eligible trials included MTTs in the intervention arm, with comparator arms comprising other systemic treatments or placebo i.e no active treatment. Outcomes of interest included HRQoL endpoint inclusion, types of HRQoL assessments, and reporting patterns. For trials listing HRQoL as an endpoint, compliance with CONSORT-PRO guidelines (Calvert et al., 2013) was evaluated. Results: We identified 61 RCTs involving 21,103 participants. Among these, 35 trials (57.4%) included HRQoL as an endpoint, with 29 (47.5%) listing it as a secondary endpoint and 6 (9.8%) as an exploratory endpoint. HRQoL was not designated as a primary endpoint in any trials. Overall, from these 35 studies, 17 (48.6%) published their QoL data in the primary publication. The most studied cancer types were breast (20%), while urothelial cancer was the least studied (2.9%). The EORTC-QLQ-C30 questionnaire was reported in 19 out of 35 trials, with the remaining 16 trials utilized site-specific HRQoL instruments. The average baseline completion rate for HRQoL assessments was 73.3% (4,837/6,603 participants). Information on HRQoL assessment completion rates was missing in 9 out of 26 trials and none of the 35 trials adhered to CONSORT-PRO guidelines for reporting methods to handle missing data. Interestingly, 22 (85%) of the trials with reported HRQoL data had statistically significant outcomes with MTTs, while 4 (15%) had non-significant outcomes. Trials with significant outcomes had a shorter median time to HRQoL data reporting (295.2 days, range: 0–3167 days) compared to those with non-significant outcomes (583.5 days, range: 0–882 days). Conclusions: Overall, we observed significant under-reporting of quality of life and patient-reported outcomes in trials assessing MTTs in heavily pretreated cancer populations. Future RCTs designs should prioritising HRQoL reporting as it is a clinically meaningful outcome.