Despite greater attention being given to treatment effects on patient wellbeing, the high heterogeneity of methodologies still limits the usefulness of QoL assessment
Quality of life (QoL) data are often communicated with significant delays compared to efficacy data, and access to the full report may take several years following the initial publication. I am glad to see that at the ESMO Gastrointestinal Cancers Congress, QoL data from two important phase III clinical trials using immunotherapy - CheckMate 8HW (Abstract 1O) and CheckMate 9DW (Abstract 148O) - were promptly presented, approximately less than one year after their respective efficacy reports.
This is a good practice, and I would encourage all study authors to do the same for the benefit of the whole gastrointestinal cancer community.
QoL data reporting has been gaining momentum in oncology since longer survivals have been achieved in both curative and non-curative settings, making it necessary to weight the reported immunotherapy benefits against the patient wellbeing - how good is an increase in survival should be calculated in terms of how much a treatment helps our patients to live better.
Measuring QoL outcomes in clinical trials is complex. In 2023, the ESMO-Magnitude of Clinical Benefit Scale (MCBS) incorporated a checklist to evaluate QoL outcomes (Ann Oncol. 2023 Apr;34(4):431-439). During the development of the checklist, the ESMO team acknowledged that researchers use several instruments with a high heterogeneity of methodologies to report QoL data in clinical trials. This holds true also for the two abstracts presented in Barcelona.
In the CheckMate 8HW, nivolumab plus ipilimumab demonstrated to prolong progression-free survival compared to chemotherapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) (N Engl J Med. 2024 Nov28;391(21):2014-2026). The immunotherapy combination also showed a significant overall survival benefit versus lenvatinib or sorafenib and manageable safety in patients with previously untreated unresectable hepatocellular carcinoma (uHCC) (Lancet. 2025 May24;405(10492):1851-1864).
Health-related QoL analysis from the CheckMate 8HW reported global health status (GHS) from EORTC QLQ-C30, while in the Checkmate 9DW the risk of deterioration from FACT-hepatobiliary questionnaire was assessed. In both abstracts, positive QoL outcomes were reported. However, none of the studies set QoL as primary or overall/global QoL as secondary endpoint: overall or global QoL were exploratory endpoints, and exclusively, time to deterioration using the FACT hepatobiliary instrument was a predefined secondary objective.
Despite in the two studies the efficacy data may have a meaningful clinical impact in tumour types that historically have bad prognosis, with no apparent detrimental effect on patients’ wellbeing, QoL findings, although of high relevance, are limited due to the selected methodology.
Since regulators are more and more encouraging the use of QoL measures and patient reported outcomes (PROs) in cancer research, there is a clear need for their more robust and comparable implementation in clinical trial design. QoL should be considered a secondary endpoint - when not primary - rather than an exploratory endpoint, as it may have important implications not only in terms of patient wellbeing, but also for regulatory decisions and reimbursement. With the introduction of the ESMO-MCBS QoL scoring system and the recent publication of the ESMO-MCBS version 2 (Ann Oncol. 2025 May21:S0923-7534(25)00166-8), ESMO advocates for greater attention from researchers to the incorporation of QoL assessment into study protocols.
