ASCO 2023: CABOSUN II: Results from a Phase 2, Open-Label, Multi-Center Randomized Study of Cabozantinib vs. Sunitinib for Non-Clear Cell RCC

( The 2023 ASCO annual meeting included a kidney cancer session, featuring a presentation by Dr. Andrew Johns discussing results of CABOSUN II, a phase 2, open-label, multi-center randomized study of cabozantinib vs. sunitinib for non-clear cell RCC. Unlike clear-cell RCC, non-clear cell histology are a diverse group of rare diseases with limited data to guide treatment. Cabozantinib is highly effective in clear cell RCC, but it is unknown whether it is superior to sunitinib, the historic standard of care for metastatic non-clear cell RCC. The objective of this phase 2 trial was to assess the efficacy of cabozantinib vs. sunitinib for non-clear cell RCC.

CABOSUN II (NCT03541902) was a randomized phase II study at 3 centers for patients with metastatic non-clear cell RCC. There were 60 patients planned to assess whether cabozantinib is better than sunitinib with a 1-sided test; patients were randomized 1:1 to cabozantinib 60mg daily or sunitinib 50mg daily (4 weeks on, 2 weeks off). Of note, sunitinib dose modification to 2 weeks on, 1 week off was allowed for toxicity. Stratification was by papillary RCC versus non-papillary RCC, good/intermediate versus poor risk disease by IMDC criteria, and prior TKI use. The primary outcome was progression-free survival by RECIST v1.1 compared between the 2 arms using the log-rank test. Secondary outcomes were objective response rate, overall survival, and adverse event rates.

 There were 32 patients randomized to cabozantinib (n = 15) or sunitinib (n = 17) between September 2018 and June 2021. Importantly, the trial stopped early due to a change in standard therapy for papillary RCC not based on these patients’ outcomes. Baseline characteristics between the two arms were as follows:

CABOSUN population characteristics 
Age range was 22-88 years with medians of 57 and 61 years for cabozantinib and sunitinib, respectively. Patients were primarily white (84%) and male (72%), with good/intermediate risk (88%), and these were balanced between arms. Non-papillary RCC were chromophobe (n = 6; 5 randomized to sunitinib), unclassified (n = 5), and MiT family translocation (n = 3; all randomized to cabozantinib). With a median follow-up of 33.3 months and 20 progression-free survival events, median progression-free survival for cabozantinib vs. sunitinib was 8.2 vs. 13.8 months (1-sided p=0.96). There were no statistically significant differences in objective response rate or overall survival between the arms, and adverse events were in line with previous studies:

CABOSUN 2 survival recurrence table

Correlative molecular analyses are currently ongoing.

Dr. Johns concluded his presentation discussing results of CABOSUN II, a phase 2, open-label, multi-center randomized study of cabozantinib vs. sunitinib for non-clear cell RCC with the following take-home messages:

  • Cabozantinib was not superior to sunitinib for metastatic non-clear cell RCC in this study
  • Both arms had high rates of stable disease or better
  • Despite stratification by papillary RCC or non-papillary RCC, there were major differences in non-papillary RCC subtypes between the arms that may have impacted the results
  • More patients with chromophobe histology, an often indolent subtype, received sunitinib while all patients with MiT family translocation, a relatively aggressive subtype, received cabozantinib
  • Permitted sunitinib dose modifications may have also influenced outcomes
  • While the PAPMET study showed cabozantinib to be superior to sunitinib for papillary RCC, optimal treatments for rare, non-papillary RCC remain a pressing need
  • Diverse disease biology among non-papillary RCC subtypes presents an important challenge for design of future trials.

Presented by: Andrew Johns, MD, The University of Texas MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.