Adjuvant immune checkpoint inhibitors (ICIs) are being investigated to reduce relapse in intermediate- or high-risk resected renal cell carcinoma (RCC). While disease-free survival and overall survival remain primary endpoints, the distinct toxicity profile of ICIs and the potential for chronic immune-related adverse events (irAEs) mean that their effects on health-related quality of life (HRQoL) must be understood.
Existing patient-reported outcome measures (PROMs) commonly used in oncology (for example, EORTC QLQ-C30, EQ-5D, FACT instruments) were developed before widespread immunotherapy use and may not capture ICI-specific or persistent toxicities. To explore HRQoL impacts beyond standard questionnaires, a qualitative interview sub-study was embedded within the international phase III RAMPART trial among UK participants.
This qualitative study used a critical realist approach to examine participant accounts as real experiences shaped by individual context. The research team combined oncology clinicians and non-clinical qualitative researchers. A patient and public involvement (PPI) representative contributed to study materials and the interview guide, which was piloted with a patient.
Participants were eligible if they were enrolled at UK RAMPART sites and randomized to Arm B (durvalumab 1500 mg every 4 weeks for 1 year) or Arm C (durvalumab same schedule plus tremelimumab 75 mg on day 1 and week 4). Sampling was purposive to ensure diversity across age, gender, trial arm, toxicity experience, and recurrence status. Ethical approval was obtained and written informed consent provided by all participants.
Between September 2024 and March 2025, 71 of 220 eligible RAMPART participants were invited; recruitment closed early due to high interest. Of 37 who expressed interest, 23 were interviewed. Median age was 57 years (range 41–76); 14 participants were male and 9 female; all identified as White. Twelve participants were in the durvalumab plus tremelimumab arm and 11 in the durvalumab monotherapy arm. Four participants had experienced recurrence.
Treatment completion data from the RAMPART dataset showed that all interviewees had completed trial treatment at the time of interview. Ten received all planned treatment; 13 (57%) discontinued early (ten due to toxicity, two due to COVID-19 disruption, one by patient choice). All participants reported at least one adverse event; 12 (52%) had grade ≥3 toxicity. Common grade ≥3 AEs included laboratory abnormalities (9/23, 39%), gastrointestinal events (5/23, 22%), and endocrine events (2/23, 9%). Median AE duration was 29 days (IQR 8–118), and 15 participants (65%) had unresolved AEs at the data cut-off. Nine participants (39%) received corticosteroids; one required additional immunosuppressive therapy for immune-mediated myasthenia gravis.
Semi-structured interviews were conducted by the same interviewer via Microsoft Teams, telephone, or in person, with a flexible guide that included vignettes illustrating severe or chronic irAEs. Interviews were recorded, transcribed, anonymised, and analysed using the framework method with NVivo14 for data management. Thematic frameworks were developed iteratively, charted by domain and case, and discussed in multidisciplinary data clinics. Transcripts were not returned to participants for member checking.
Participants described a range of physical and psychological changes during and after ICI treatment. A central finding was that the duration and chronicity of irAEs often mattered more to participants’ lived experience than the peak clinical severity. Even persistent low-grade toxicities could substantially disrupt daily life.
Fatigue emerged as the most common and debilitating chronic symptom, described by participants as “bone deep” and unpredictable; it limited activities and reduced the ability to push through tiredness. Persistent arthralgia affected mobility and comfort for several participants, with some experiencing intermittent pain and others ongoing widespread discomfort that interfered with routine tasks. Chronic gastrointestinal symptoms such as diarrhoea were also reported as disruptive to daily functioning.
Beyond physical symptoms, cognitive changes and emotional strain were frequently reported. Participants described anxiety about symptom unpredictability, uncertainty regarding recovery, and emotional burden associated with altered capabilities. The cumulative effect of persistent symptoms eroded quality of life even where symptoms were not classified as high grade clinically.
Interviewees emphasised that the real-world impact of irAEs was moderated by personal circumstances. Employment status, financial security, caregiving responsibilities, and social support influenced how toxicities affected day-to-day life.
For some, work demands or caring roles magnified the consequences of persistent fatigue or pain, affecting ability to fulfil responsibilities and threatening income. Conversely, supportive relationships, flexible work arrangements, and structured clinical follow-up mitigated burden and helped participants adapt to lasting effects.
Participants also reported strategies to accommodate lingering symptoms, such as pacing activities and reorganising priorities. However, the unpredictable or fluctuating nature of some irAEs increased uncertainty, sometimes affecting mental health and future planning.
Findings indicate that standard trial PROMs and assessment schedules may fail to capture the full spectrum of ICI-related survivorship issues, particularly chronic, fluctuating, or late-onset toxicities. Reporting solely peak toxicity grade may obscure the lasting functional and psychosocial impact experienced by patients.
The study authors argue that clinical trials evaluating ICIs should report not only toxicity grade but also the duration and resolution status of AEs to better inform patients and clinicians about likely trajectories and long-term consequences. Clear survivorship care pathways for management of chronic irAEs and accessible multidisciplinary support were identified as important to mitigate ongoing burden.
Preliminary recommendations were drafted from analysis and refined in a PPI workshop with ten interview participants. A multidisciplinary expert panel then reviewed recommendations for clinical relevance and feasibility. Core recommendations included improved trial reporting of AE duration and resolution, development of ICI-specific HRQoL tools that capture persistent irAEs, and establishment of clear care pathways for chronic toxicity management. Details of the co-developed recommendations are presented alongside the study findings in the original report.
The purposive sample achieved diversity across several predefined characteristics, but ethnicity targets were not met: all participants identified as White. Only two participants aged ≥75 were recruited despite a target of three. Transcripts were not returned to participants for member checking. Interview data reflect UK RAMPART participants and may not capture experiences in other settings.
This qualitative sub-study within RAMPART found that chronic and persistent immune-related adverse events from adjuvant durvalumab with or without tremelimumab can have enduring negative effects on HRQoL, mental health, and work ability. Participants frequently rated the duration and chronicity of toxicities as more impactful than peak severity. To inform patient decision-making and survivorship care, trials should report toxicity grade alongside duration and resolution; development of ICI-specific HRQoL instruments and clear care pathways for chronic irAEs are needed.