Trial results for the Phase 3 study (NCT03755791) investigating atezolizumab in combination with cabozantinib for advanced hepatocellular carcinoma (HCC) were posted on ClinicalTrials.gov on 2025-12-11. The combination therapy demonstrated a median progression-free survival (PFS) of 6.80 months, compared to 4.21 months for sorafenib.
Background
Advanced hepatocellular carcinoma (HCC) is a challenging malignancy. This study investigated a new combination therapy against the current standard of care, sorafenib, for patients who had not received previous systemic anticancer therapy.
Trial design
The Phase 3 study (NCT03755791), titled "Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Participants With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Received Previous Systemic Anticancer Therapy," enrolled 837 participants. The trial evaluated cabozantinib in combination with atezolizumab against sorafenib as a control arm in adults with advanced hepatocellular carcinoma (HCC) who had not received previous systemic anticancer therapy. An additional arm investigated single-agent cabozantinib to assess its contribution to the combination's efficacy and safety. The study assessed outcomes including progression-free survival (PFS) and overall survival (OS).
Key results
The trial results showed differences in progression-free survival (PFS) and overall survival (OS) between the treatment arms.
For Progression Free Survival (PFS) in the PFS Intent to Treat (PITT) Population:
- The experimental arm, receiving cabozantinib in combination with atezolizumab, had a median PFS of 6.80 months.
- The control arm, receiving sorafenib, had a median PFS of 4.21 months.
A Log Rank analysis indicated a Hazard Ratio (HR) of 0.63 (99.0% Confidence Interval: 0.44 to 0.91) with a p-value of 0.0012, favoring the combination therapy.
For the single-agent cabozantinib arm, the median PFS was 5.82 months, compared to 4.27 months for the control arm (sorafenib) in the ITT population.
For Overall Survival (OS) in the ITT Population:
- The experimental arm (cabozantinib + atezolizumab) had a mean OS of 16.46 months.
- The control arm (sorafenib) had a mean OS of 15.51 months.
A Log Rank analysis showed a Hazard Ratio (HR) of 0.99 (96.0% Confidence Interval: 0.78 to 1.24) with a p-value of 0.9056.
What this means
The results indicate that the combination of cabozantinib and atezolizumab significantly improved progression-free survival compared to sorafenib in patients with advanced hepatocellular carcinoma who had not received prior systemic therapy. The median PFS of 6.80 months for the combination versus 4.21 months for sorafenib, along with the statistically significant hazard ratio, suggests a clinical benefit in delaying disease progression. While an improvement in overall survival was observed numerically, it did not reach statistical significance in this analysis. The single-agent cabozantinib arm also showed a longer median PFS compared to sorafenib, suggesting its contribution to the combination's efficacy.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03755791, titled "Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Participants With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Received Previous Systemic Anticancer Therapy," were posted on 2025-12-11 on clinicaltrials.gov.