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Published on: May 24, 2024
Clinical Trial: Early Nivolumab Addition to Regorafenib in Patients With Hepatocellular Carcinoma in Second-Line (The
Marco Sanduzzi-Zamparelli1,2,3, Ana Matilla3,4, José Luis Lledo3,5
1BCLC Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Background & Aims:
Highly effective second-line treatments for hepatocellular carcinoma remain an unmet need. The GOING investigator-initiated Phase I/IIa trial evaluated regorafenib plus nivolumab (add-on) in patients who progressed on sorafenib (Cohort-A) or discontinued atezolizumab-bevacizumab (Cohort-B).
Methods:
Patients received regorafenib for two 28-day cycles, adding nivolumab in cycle 3, until unacceptable adverse events, symptomatic progression, withdrawal or death. Primary endpoint was safety. Secondary endpoints included overall survival, time to progression, post-progression survival, objective response rate and incidence of new-extrahepatic-spread.
Results:
Of 85 patients screened, 67 were enrolled (75.5% BCLC-C). All experienced adverse events and 9% led to discontinuation. Severe treatment-related adverse events occurred in 28.4% overall, 32.1% in Cohort-A, and 14.3% in Cohort-B. Median overall survival was 20.0 (95% CI 11-37) months, with 40.6% survival at 36 months. In Cohort-A, median overall survival was 25 (95% CI 14-39) months with 45% survival at 36 months, while Cohort-B median overall survival was 8 (95% CI 4-NE) months with 28.6% survival at 24 months. Objective response rate was 16.4%; median time to progression and post-progression survival were 5 (95% CI 4-9) months and 14 (95% CI 8-33) months. Intrahepatic growth was the most common progression pattern, followed by new-extrahepatic-spread.
Conclusions:
The add-on strategy of regorafenib plus nivolumab in second-line had manageable safety and significant clinical activity with a noteworthy median overall survival of 20 months. Among those progressing on sorafenib, 45% were alive at 3 years. These findings support further evaluation with mechanism-guided trials after progression on immunotherapy.
Trial Registration:
EudraCT number: 2019-003108-10; https://www.clinicaltrialsregister.eu.
Insights
Regorafenib plus nivolumab showed manageable safety and significant clinical activity in second-line hepatocellular carcinoma treatment. This combination therapy resulted in a median overall survival of 20 months, with 45% of patients alive at 3 years after progressing on sorafenib.
Area of Science:
- Hepatobiliary Cancers
- Medical Oncology
- Clinical Trials
Background:
- Hepatocellular carcinoma (HCC) lacks effective second-line treatments.
- The GOING trial investigated regorafenib plus nivolumab as a novel therapeutic strategy.
Purpose of the Study:
- To evaluate the safety and clinical activity of regorafenib plus nivolumab in HCC patients.
- To assess overall survival, time to progression, and response rates in two distinct patient cohorts.
Main Methods:
- Phase I/IIa trial involving 67 HCC patients progressing on sorafenib or atezolizumab-bevacizumab.
- Regorafenib was administered for two cycles, followed by the addition of nivolumab.
- Safety, overall survival, time to progression, and objective response rate were primary and secondary endpoints.
Main Results:
- The combination therapy demonstrated manageable safety with severe adverse events in 28.4% of patients.
- Median overall survival was 20 months (40.6% survival at 36 months).
- Patients progressing on sorafenib (Cohort-A) had a median overall survival of 25 months, with 45% alive at 3 years.
Conclusions:
- Regorafenib plus nivolumab offers a promising second-line treatment option for HCC with significant clinical activity.
- The observed median overall survival of 20 months highlights the potential of this combination therapy.
- Further mechanism-guided trials are warranted to explore this strategy in patients progressing on immunotherapy.
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