ABSTRACT
BACKGROUND: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. METHODS: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. RESULTS: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). CONCLUSION: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.
ABSTRACT
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide with a poor prognosis. Treatment with immune checkpoint inhibitors (ICIs) has improved overall survival in patients with HCC. However, not all patients benefit from the treatment. In this study, 59 patients with HCC were enrolled from two medical centers in Saudi Arabia, with 34% using antibiotics concurrently with their Nivolumab (anti-PD1 blockade). The impact of antibiotic use on the clinical outcomes of patients with HCC undergoing treatment with anti-PD1 blockade was examined. The patients' overall survival (OS) was 5 months (95% CI: 3.2, 6.7) compared to 10 months (95% CI: 0, 22.2) (p = 0.08). Notably, patients with Child-Pugh A cirrhosis receiving anti-PD1 blockade treatment without concurrent antibiotic use showed a significantly longer median OS reaching 22 months (95% CI: 6.5, 37.4) compared to those who were given antibiotics with a median OS of 6 months (95% CI: 2.7, 9.2) (p = 0.02). This difference in overall survival was particularly found in Child-Pugh class A patients receiving anti-PD1 blockade. These findings suggest that antibiotic use may negatively affect survival outcomes in HCC patients undergoing anti-PD1 blockade, potentially due to antibiotic-induced alterations to the gut microbiome impacting the anti-PD1 blockade response. This study suggests the need for careful consideration when prescribing antibiotics to patients with HCC receiving anti-PD1 blockade.