Elizabeth Nally, MBBS, on decision regret and toxicity perception with adjuvant pembrolizumab

In this video, Elizabeth Nally, MBBS, discusses findings presented at the 2026 American Society of Clinical Oncology Annual Meeting examining decision regret and toxicity perceptions among patients with renal cell carcinoma (RCC) who received adjuvant immune checkpoint inhibitor therapy.¹ Nally is a clinical research fellow at Barts Cancer Institute in London.

Although adjuvant pembrolizumab has demonstrated a significant survival benefit in RCC,² Nally noted that clinical trials have not consistently demonstrated a meaningful deterioration in quality of life despite the potential for long-term immune-related adverse events (irAEs). The study explored whether conventional toxicity grading may underestimate the impact of these adverse events on patients’ lives and ultimately their perceptions of treatment.

The analysis included 104 patients with RCC who received adjuvant pembrolizumab (Keytruda) across 3 tertiary cancer centers in London. Investigators used the validated Ottawa Decision Regret Scale alongside a patient-informed framework that categorized irAEs as life-changing, significant, or non-significant. The findings demonstrated a disconnect between conventional CTCAE grading and patients’ experiences: 33% of grade 1 to 2 toxicities were considered significant by patients, and patient-reported toxicity was not associated with grade 3 or higher CTCAEs (P = .11). Further, there was no significant difference in regret between patients that experienced CTCAE grade 1-2 irAEs vs grade 3 to 4 irAEs (14.9 vs 15.1; P = .23).

Overall, 13% of patients expressed treatment regret, with regret substantially higher among those reporting life-changing or significant toxicity (26.9 LC v 26.1 S v 2.1 NS; P = .0021). Permanent endocrine (DRS 28.8 v 9.5; P = .003) and musculoskeletal irAEs (DRS 25.1 v 12.8; P = .042) were particularly associated with greater regret.

According to Nally, the findings highlight the limitations of relying solely on CTCAE grading when discussing the potential risks and benefits of adjuvant immunotherapy. Although CTCAE remains important for identifying acute and potentially life-threatening toxicities, it may not adequately capture the long-term effects of immune-related adverse events on patients’ daily lives. Nally emphasized that counseling around adjuvant pembrolizumab should acknowledge both its survival benefit and the possibility of persistent toxicity, with treatment decisions tailored to individual patient preferences and expectations.

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