Patient and Physician Preferences for Treatment in Advanced Renal Cell Carcinoma in Asia-Pacific (PEAR)- A Discrete Choice Experiment

Technical Summary: Patient and Physician Preferences for Treatment in Advanced Renal Cell Carcinoma in Asia-Pacific (PEAR)

Problem Statement
The treatment landscape for first-line advanced renal cell carcinoma (1L aRCC) has shifted from tyrosine kinase inhibitor (TKI) monotherapy to immune checkpoint inhibitor (ICI)–based combinations. While these regimens offer improved efficacy, they introduce complex trade-offs regarding adverse event profiles, dosing schedules, and survival benefits. Existing data on treatment preferences within the Asia-Pacific (APAC) region are limited, with most discrete choice experiments (DCEs) conducted in the United States or prior to the widespread adoption of ICI-based combinations. Furthermore, there is a lack of regional evidence comparing the benefit-risk trade-offs preferred by patients versus physicians, which is critical for facilitating shared decision-making in diverse healthcare systems.

Methodology
This study employed a cross-sectional, online discrete choice experiment (DCE) to quantify treatment preferences among 81 aRCC patients and 75 physicians across Australia, Hong Kong, and South Korea.

• Study Design: Two survey versions were developed (lay language for patients, clinical terminology for physicians) following ISPOR good research practices. The DCE instrument was refined through qualitative interviews with 10 patients and 16 physicians, followed by cognitive interviews with 11 patients and 12 physicians to ensure clarity.
• Attributes and Levels: Seven attributes were selected: Progression-Free Survival (PFS), Overall Survival (OS) at 3 years, Complete Response (CR), Duration of Response (DoR), chance of hospitalization due to side effects, Grade 3/4 pneumonitis, and Grade 3/4 gastrointestinal (GI) perforation.
• Experimental Design: A D-efficient fractional factorial design generated 15 choice tasks per respondent, including one dominant choice set for internal validity.
• Statistical Analysis: A mixed logit regression model was used to estimate preference weights. Relative Importance (RI) scores were calculated to determine the contribution of each attribute to decision-making. Maximum Acceptable Risk (MAR) analysis quantified the risk tolerance of respondents regarding adverse events in exchange for efficacy gains. Subgroup analyses were conducted by region, age, treatment duration, and prior side effect experience.

Key Results

• Demographics: The patient cohort (median age 63) was predominantly male (84%) and Asian (75%), with 73% reporting treatment-related side effects. The physician cohort (55% with ≥16 years of experience) consisted primarily of medical oncologists (49%) and urologists (36%).
• Preference Weights and Relative Importance:
  • Patients: The most critical attribute was Grade 3/4 pneumonitis (23% RI), followed by DoR (19%), OS at 3 years (18%), and CR (17%). PFS contributed minimally (2%). Patients exhibited strong negative utility for safety risks.
  • Physicians: The most critical attribute was OS at 3 years (29% RI), followed by DoR (26%), CR (15%), and PFS (14%). Risk attributes (pneumonitis, GI perforation, hospitalization) held low importance (2–7% RI) for physicians compared to patients.
• Maximum Acceptable Risk (MAR): A significant divergence in risk tolerance was observed. Physicians were willing to accept substantially higher risks for efficacy gains. For example, to achieve a 20–30% improvement in 3-year OS, physicians accepted an additional 52% risk of Grade 3/4 pneumonitis, whereas patients accepted only 2–4%. Similar disparities were noted for GI perforation and improvements in CR and DoR.
• Subgroup Findings: South Korean patients showed higher preference for longer PFS compared to other regions. Younger patients (<65 years) demonstrated greater aversion to GI perforation risks than older patients. Patients on treatment for ≤12 months preferred longer DoR and lower pneumonitis risk compared to those on treatment >12 months.

Significance and Claims
The paper claims that while both patients and physicians in the APAC region prioritize survival outcomes, they diverge significantly in their benefit-risk trade-offs. Physicians prioritize efficacy and demonstrate higher risk tolerance, likely influenced by clinical experience and confidence in managing adverse events. In contrast, patients are more risk-averse, placing greater emphasis on safety and tolerability.

The study concludes that these differences highlight the necessity of integrating patient preferences into shared decision-making frameworks. The authors assert that bridging the gap between physician-driven efficacy goals and patient-driven safety concerns is essential for achieving value-based care in 1L aRCC. The study positions itself as one of the first DCEs in the APAC region to directly compare patient and physician preferences for 1L aRCC, providing region-specific evidence to inform patient-centered care.

Limitations
The authors acknowledge limitations including small sample sizes limiting local-level conclusions, potential selection bias toward engaged patients, the exclusion of cost and quality-of-life as standalone attributes, and the restriction of participation to those with internet access. Additionally, the study notes that treatment attributes were based on knowledge at the time of study initiation, and perspectives may have evolved.