A phase III study testing the role of proactive coaching on patient reported outcome in advanced or metastatic renal cell carcinoma treated with sunitinib or a combination of axitinib + pembrolizumab or avelumab in first line therapy (PREPARE; AIO-NZK-0115/ass).
Authors: Viktor Grünwald, Lutz Jacobasch, Maike de Wit, Severine Banek, Guenter Niegisch, Mark-Oliver Zahn, Andreas Neisius, Phillip Marks, Mirko Müller, Ludwig von Weikersthal, Andreas Huebner, Marinela Augustin, Eyck von der Heyde, Christian Thomas, Nils Gilbert, Alexander Fehr, Heribert Stauder, Ursula Vehling-Kaiser, Ralf Eckert, Philipp Ivanyi
Journal: Journal of Clinical Oncology (2025)

523 Background: Tyrosine kinase (TKI) and immune checkpoint inhibitors (CPI) are first-line options in metastatic renal cell carcinoma (mRCC). Most patients (pts) experience adverse events (AE) and 20-30% discontinue therapies due to AEs. We tested whether proactive onco-coaching (POC) improved quality of life (QoL) in patients with medical treatment. Methods: Adult treatment-naïve mRCC pts who were candidates for sunitinib (SU), axitinib + avelumab (AA) or axitinib + pembrolizumab (AP) were eligible. Treatment and modifications were at the physician's discretion. Pts were 1:1 randomized to POC by a trained nurse (8 visits of structured interviews educating on preventive, preemptive and supportive measures, and phone call follow-up for a total of 24 wks) or standard of care (SOC). Primary endpoint was the fraction of pts with QoL improvement (QOLI) by ≥3 points (minimal important difference: MID) of the FKSI-15 score. Secondary endpoints consisted of patient reported outcomes (PRO: FACT-G, EQ-5D), time to QOLI, efficacy, survival and safety (CTCTAE 4.03). The planned sample size was 430 pts. Log rank analyses were employed for time to event endpoints and Fisher exact tests for categorical data. Results: Between 2016 and 2023, 113 pts were included. Median age was 72 and 68y (POC vs. SOC). 44% had a Charlson Comorbidity Index (CCI) ≥2. MSKCC good/intermediate/poor risk were 21/61/12%. 86% had clear cell histology. Of 110 treated patients, 39% and 61% received SU or AXI-CPI (AA or AP). FKSI-15-completion rate was 85%. 80 pts (73%) had ≥2 PRO assessments and were evaluable for the primary endpoint. There was no difference in QOLI between POC and SOC (43.6% vs. 41.5%; p=0.95). Mean baseline FKSI-15 score was similar between arms, as were ORR (38.2 [95% CI 25.4-52.3] vs. 34.5% [95% CI 22.2-48.6]; p=0.96) and PFS (11.1 [95% CI 8.3- 18.9] vs. 9.2 mo [95% CI 5.6-14.6]; p=0.21). Overall survival was favored by POC (median 49.6 [95% CI 30.6- 61.6] vs. 25.4 mo [95% CI 17.8-NC]; p=0.11). Stratification by CCI had no relevant effect on OS in the POC arm (p=0.26), while pts. with CCI ≥2 had poorest OS in the SOC arm (15.7 vs. 33.4 mo; p=0.002). Treatment related AEs of any or ≥3 grade affected 96.4% and 52.7% with POC and 85.5% and 36.4% with SOC. Discontinuation due to toxicity between POC vs. SOC occurred for TKI in 7.3 vs. 9.1% and for CPI in 18.2 vs. 5.5% pts. Conclusions: Target patient accrual was not reached, and POC did not improve the rate of QoL responders or treatment efficacy. However, there was a trend towards a considerable extension of OS in the POC group, suggesting an overall beneficial impact of proactive coaching compared to standard reactive therapy management. Comorbid patients putatively benefit most from pro-active coaching, which warrants further studies. Clinical trial information: NCT03013946 .