Adjuvant I-O Combination Tied to Early QoL Declines in RCC

While adjuvant durvalumab plus tremelimumab aims to extend disease-free survival in resected renal cell carcinoma (RCC), the phase 3 RAMPART trial (NCT03288532) suggests this benefit may come with a noticeable near-term cost to patient well-being.

Adjuvant therapy with durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) in patients with resected RCC was associated with early reductions in patient-reported quality of life (QoL), according to findings from the trial presented at the 2026 ASCO Genitourinary Cancers Symposium.

Participants receiving the combination therapy reported meaningful declines in overall health, role functioning, fatigue, and insomnia at week 16. Although many early deficits improved by month 15, new declines emerged in cognitive function and pain, emphasizing the need to consider patient-reported outcomes alongside disease-free survival (DFS) when evaluating the overall impact of treatment.

“These findings should be considered alongside the DFS benefit when interpreting the trial results, lead study author and presenter,” Sophie Merrick, MD, emphasized at the conference.

She is a senior clinical Research Fellow at the University College London (UCL), MRC Clinical Trials Unit at UCL, in England.

RAMPART Trial Shows DFS Benefit

RAMPART is an international, investigator-led, open-label, phase 3 trial evaluating adjuvant immune checkpoint therapy vs active monitoring in patients with resected RCC at intermediate or high risk of recurrence. Patients were randomized in a 3:2:2 ratio to active monitoring (n = 340), durvalumab monotherapy (n = 225), or durvalumab plus tremelimumab (n = 225).

In the intention-to-treat population, durvalumab and tremelimumab improved DFS compared with active monitoring. Three-year median DFS was 81% with durvalumab plus tremelimumab versus 73% in the active monitoring arm (HR, 0.65; 95% CI, 0.45-0.93; P = .0094).

“Evaluating QoL is essential to understanding the overall impact of treatment,” said Merrick said, emphasizing the need to understand the patient experience.

Study Design and Patient-Reported Outcomes Assessment

The RAMPART QoL sub-study was conducted as an optional component in English-speaking countries, including the UK and Australia. Patient-reported outcomes (PROs) were collected using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline, week 16, and month 15, with a 7-day recall period.

A total of 329 participants consented to the sub-study, of whom 254 (104 durvalumab plus tremelimumab, 150 active monitoring) completed baseline and at least one follow-up questionnaire, making them eligible for PRO analysis. Analyses were exploratory and adjusted for baseline score and sex, with no correction for multiple testing.

The primary PRO end point was the change in overall health and QoL from baseline to month 15. Secondary outcomes included change from baseline to week 16, changes in five functional domains, nine symptom and single-item scales, and the proportion of participants experiencing improvement, stability, or deterioration in overall QoL at each time point.

Baseline characteristics of patients enrolled in the QoL sub-study were broadly similar to those of the overall trial population. Within the sub-study cohort, baseline characteristics between the durvalumab plus tremelimumab arm and the active monitoring arm were also generally balanced.

A slightly higher proportion of patients in the durvalumab plus tremelimumab arm were male (74% versus 68% in the active monitoring arm), the presentation noted. Regarding performance status, 88% and 12% of patients in the durvalumab plus tremelimumab arm had an ECOG performance status of 0 and 1 compared with 80% and 12% in the active monitoring arm, respectively.

Safety Tolerability of the Combination

Safety data from the durvalumab plus tremelimumab arm mirrored previous reports of adjuvant checkpoint therapy. Any-grade adverse events (AEs) occurred in 97% of durvalumab plus tremelimumab participants versus 63% in the active monitoring group. Grade 3 or higher AEs occurred in 40% of durvalumab plus tremelimumab recipients compared with 8% in active monitoring.

Treatment discontinuation due to AEs was reported in 32% of patients receiving DT, and 36% required systemic corticosteroids. Serious AEs were reported in 34% of the durvalumab plus tremelimumab arm and 6% of the active monitoring arm. Treatment-related deaths were rare (occurred in less than 1% of the population).

Common immune-related AEs in the durvalumab plus tremelimumab arm included fatigue, diarrhea, colitis, pneumonitis, hypothyroidism, and dermatologic toxicity. While AEs were largely manageable, these events are relevant to interpreting early declines in patient-reported QoL, particularly functional and symptom domains.

Trends in QoL and Symptom Burden

Change in overall health and QoL from baseline to month 15 showed no statistically significant or clinically meaningful difference between treatment arms. Among the subset of participants who completed the EORTC QLQ-C30 questionnaire at both baseline and month 15, 59 patients

in the durvalumab plus tremelimumab arm and 77 patients in the active monitoring arm were evaluable for this analysis.

However, at week 16, patients receiving durvalumab plus tremelimumab reported clinically meaningful reductions in overall health and QoL, role functioning, and higher fatigue and insomnia scores compared with active monitoring. The odds of a large reduction in QoL at week 16 were significantly higher with durvalumab plus tremelimumab (95% CI, 1.9-7.1; P = .0001).

By month 15, many early deficits improved, with overall health and role functioning approaching baseline levels. However, new, clinically meaningful declines in cognitive function and pain were observed.

Limitations

The QoL sub-study was limited by its optional design and open-label nature. Additionally, analyses were exploratory and conducted in a subset of the overall trial population. Completion rates declined over time, although follow-up was similar between arms.

Reference

Merrick S, Murphy L, Frangou E, et al. Patient-reported outcomes in resected renal cell carcinoma: Active monitoring vs. durvalumab and tremelimumab in the RAMPART trial. J Clin Oncol. 2026;44(suppl 7):420. doi: 10.1200/JCO.2026.44.7_suppl.420.