KEY TAKEAWAYS
- The JAVELIN Renal 101 trial (phase 3) (NCT02684006) demonstrated that CRP levels at baseline and early after treatment with A + Ax may predict outcomes in patients with aRCC, specifically those with IMDC poor risk.
- Patients with IMDC poor risk who had prolonged PFS and OS were observed at the third interim analysis of OS.
- Patients in the A + Ax arm with 3 or 4-6 IMDC risk factors were categorized into subgroups with CRP normal, normalized, or non-normalized. CRP levels were assessed at screening and on day 1 of each 6-week cycle.
- The results suggested that patients with poor-risk aRCC treated with A + Ax who had low CRP levels at baseline and during treatment or a rapid decrease in high CRP levels might have favorable long-term outcomes.
Patient outcomes with A + Ax in aRCC may be predicted by CRP levels at baseline (BL) and early after therapy, according to analyses from the phase 3 JAVELIN Renal 101 study (NCT02684006). Nevertheless, at the third interim analysis of OS, several patients with International Metastatic RCC Database Consortium (IMDC) low risk experienced long periods of progression-free survival (PFS) and overall survival (OS). They looked at how CRP levels correlated with improved PFS/OS for patients with IMDC low risk who received A + Ax.
The screening and the first day of each 6-week cycle were used to measure CRP levels. In the A + Ax group, patients with 3 or 4-6 IMDC risk factors were divided into subgroups based on whether their CRP was normal (BL CRP 10 mg/L), normalised (BL CRP 10 mg/L and 1 CRP value decreased to 10 mg/L during 6-week treatment), or non-normalized (CRP 10 mg/L at BL and during 6-week treatment). Patients with a longer PFS/OS (PFS >24 months [mo] and OS >30 mo) or PFS 24 months [mo] had their CRP levels compared (any OS duration).
For the A + Ax group (N=442), 7 patients had improved PFS/OS and 5 patients had PFS >24 months among those with 3 or more IMDC risk factors (Table). Patients who had 3 or more risk factors and experienced a prolonged PFS/OS tended to be in the normal or non-normalized CRP group. The median CRP levels were 1 mg/dL at BL and maintained 1 mg/dL over 24 months in patients with 3 risk factors and improved PFS/OS.
CRP levels were high at BL, but fell significantly within 6 weeks, and were sustained for 24 months, in patients with 4-6 risk factors and improved PFS/OS. A low CRP level at BL and during treatment, or a rapid decline in high CRP levels, may predict better long-term results in patients with poor-risk aRCC treated with A + Ax, while CRP levels are nonspecific and may increase/reduce with other diseases/comorbidities.
Source: https://meetings.asco.org/abstracts-presentations/216558
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02684006/
Tran, B.D., Li, J., Ly, N. et al. Cabozantinib exposure–response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. Cancer Chemother Pharmacol 91, 179–189 (2023).
