Patients with resected renal cell carcinoma who received adjuvant durvalumab (Imfinzi) with or without tremelimumab-actl (Imjudo) in the phase 3 RAMPART trial (NCT03288532) placed greater weight on the duration and chronicity of immune-related adverse effects (irAEs) compared with their severity when describing the impact on health-related quality of life (HRQOL), according to findings from a qualitative substudy published in PLOS One.1
The analysis showed that persistent toxicities such as fatigue, arthralgia, and diarrhea disrupted daily functioning, and employment, financial security, and caregiving responsibilities shaped how heavily these effects weighed on patients.
Among eligible patients enrolled in RAMPART at sites in the United Kingdom (n = 220), 71 were invited to the substudy, 37 expressed interest, and 23 were interviewed (durvalumab, n = 11; durvalumab plus tremelimumab, n = 12). All 23 patients experienced at least 1 AE of any grade, and 52% experienced grade 3 or higher toxicities. The median AE duration was 29 days (interquartile range [IQR], 8-118), and 65% of patients had unresolved AEs at data cutoff. Additionally, 57% discontinued treatment early, and interviews took place at a median of 33.4 months (range, 23.4-66.5) after treatment completion.
The most common grade 3 or higher AEs were laboratory abnormalities (39%), gastrointestinal toxicities (22%), and endocrine toxicities (9%). Early discontinuation was attributed to toxicity (n = 10), COVID-19–related disruption (n = 2), or patient choice (n = 1). Nine patients (39%) received corticosteroids, and 1 required additional immunosuppressive therapy for immune-mediated myasthenia gravis.
Fatigue was reported as the most common and debilitating chronic symptom, which patients described as "bone deep" and unpredictable, followed by diarrhea and arthralgia. Hypothyroidism was generally manageable, whereas adrenal insufficiency, which requires lifelong steroid replacement, was described as complex and burdensome; this was linked to anxiety and low mood. Asymptomatic laboratory toxicities, such as hepatotoxicity, were not perceived as affecting HRQOL. Almost half of patients reported cognitive changes, most often short-term memory decline and difficulty concentrating, and some with chronic symptomatic toxicities described severe depression and suicidal thoughts.
Patients in physically demanding or self-employed roles and those in single-income households reported greater disruption and financial strain, whereas retirement, flexible or supportive employers, family support, and structured follow-up were protective. Some patients viewed irAEs as acceptable if treatment reduced the risk of recurrence.
"Chronic irAEs can negatively affect HRQOL, mental health, and the ability to work," lead study author Sophie Merrick, MBCHB, MRCP, PhD, of the UCL Innovative Clinical Trials Unit of the Institute of Clinical Trials and Methodology, at the University College London in the United Kingdom, and coauthors wrote in the publication.
The investigator-led RAMPART platform trial evaluated adjuvant durvalumab with or without tremelimumab vs active monitoring in patients with resected RCC at intermediate or high risk of relapse. At the primary analysis, durvalumab plus tremelimumab significantly improved disease-free survival (DFS) vs active monitoring, whereas durvalumab monotherapy did not.1,2 Pembrolizumab (Keytruda) has improved DFS and overall survival in resected clear cell RCC, and the investigators noted that HRQOL is increasingly central to benefit-risk assessments of adjuvant immunotherapy.1
Eligible patients received durvalumab at 1500 mg every 4 weeks for 1 year (arm B) or the same durvalumab schedule plus tremelimumab at 75 mg on day 1 and at week 4 (arm C), and had completed at least 2 EORTC QLQ-C30 questionnaires. Patients were purposively sampled across age, gender, ethnicity, trial arm, toxicity experience, and recurrence status.
The median age was 57 years (range, 41-76); 14 patients were men, 9 were women, all identified as White, and 4 had experienced recurrence.
Semi-structured interviews (online, n = 14; telephone, n = 7; in-person, n = 2) lasted a median of 40 minutes (range, 25-78) and were analyzed using the framework method. Recommendations were refined at a workshop with 10 interviewed patients and then reviewed by a multidisciplinary expert panel.
The investigators recommended that immune checkpoint inhibitor (ICI) trials report toxicity grade together with irAE duration, resolution, and any need for lifelong treatment, and that HRQOL be assessed with validated ICI-specific patient-reported outcomes analyzed at the domain level rather than with global scores alone. Existing instruments such as the EORTC QLQ-C30 were developed before the immunotherapy era and may miss toxicities such as arthralgia, they noted.
In clinical practice, the authors called for clear ownership of long-term toxicity management across oncology, primary care, and specialty teams; written follow-up plans with a designated contact; tailored exercise and rehabilitation programs; proactive psychological support; and practical measures such as remote appointments and early financial advice.
Limitations included the UK-only cohort and a lack of ethnic diversity; only 6 (3%) of the 220 eligible patients identified as Asian (n = 5) or Black (n = 1). The sample was selected to capture a breadth of toxicity experiences and does not reflect irAE incidence in RAMPART, and the long recall period may have affected accuracy.
1. Merrick S, South A, Frangou E, et al. Health-related quality of life with adjuvant immune checkpoint inhibition in renal cell carcinoma: a qualitative study of UK participants in the phase III RAMPART trial. PLoS One. 2026;21(9):e0358789. doi:10.1371/journal.pone.0358789
2. Adjuvant Durvalumab Plus Tremelimumab Shows DFS Advantage Over Active Monitoring in Resected RCC. OncLive. Published May 30, 2026. Accessed October 15, 2026.
