Clinical Outcomes of Cabozantinib in Patients Previously Treated with Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma—Importance of Good Liver Function and Good Performance Status

Kuzuya, Teiji; Kawabe, Naoto; Ariga, Murali; Ohno, Eizaburo; Funasaka, Kohei; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Miyahara, Ryoji; Shibata, Tomoyuki; Takahara, Takeshi; Kato, Yutaro; Hirooka, Yoshiki

doi:10.3390/cancers15112952

Cited by 7 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our cohort, nivolumab showed a longer OS compared to sorafenib only despite the presence of multiple negative confounders, such as the presence of more co-morbidities, more patients with ECOG 2 status, BCLC C status, extravascular invasion, and CTP B status in the nivolumab arm. In previous analyses of patients with uHCC, CTP score, BCLC stage and performance status have been prognostically valuable to predict OS [20][21][22][23]. The survival of sorafenib-treated CTP B patients in our study (5 months) was comparable to real-life data reported from the GIDEON registry (5.2 months) [20].…”

Section: Discussionsupporting

confidence: 76%

See 1 more Smart Citation

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Sanai,

Odah,

Alshammari

et al. 2023

Preprint

View full text Add to dashboard Cite

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) in second-line nivolumab and 11.0 months (95% CI: 3.6–18.4) in 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.

show abstract

Section: Discussionsupporting

confidence: 76%

“…The relevance of maintained hepatic reserve appears crucial in prolonging survival in uHCC [21,22,25].…”

Section: Discussionmentioning

confidence: 99%

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Sanai,

Odah,

Alshammari

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In our cohort, nivolumab showed a longer OS compared to sorafenib, despite the presence of multiple negative confounders, such as the presence of more co-morbidities, more patients with ECOG 2 status, BCLC C status, extravascular invasion, and CTP B status in the nivolumab arm. In previous analyses of patients with uHCC, the CTP score, BCLC stage, and performance status have been prognostically valuable in predicting OS [ 20 , 21 , 22 , 23 ]. The survival of sorafenib-treated CTP B patients in our study (5 months) was comparable to real-life data reported from the GIDEON registry (5.2 months) [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Sanai,

Odah,

Alshammari

et al. 2024

Cancers

View full text Add to dashboard Cite

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.

show abstract

“…Thus, by adequately monitoring patients and matching the dose of lenvatinib, AEs could be safely managed, and the results suggest that this enables even advanced HCC patients with symptoms of anorexia or fatigue to experience a normal level of benefits from lenvatinib treatment. The desired effects of ICIs (e.g., atezolizumab or bevacizumab) on the immune system tend to be long-lasting, and, after treatment of HCC patients with ICIs, favorable effects have been reported for the use of the anti-VEGFR-2 monoclonal antibody ramucirumab or the multi-kinase inhibitor cabozantinib (an MTA) as second-line therapies (34)(35)(36). Our results are in line with these findings, and support the possibility of a favorable pseudo-combination therapy effect when administering agents that inhibit other cellular signaling pathways to patients who earlier received immunotherapy (37).…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes With Lenvatinib in Patients Previously Treated With Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma

MUTO,

KUZUYA,

KAWABE

et al. 2023

Anticancer Res

View full text Add to dashboard Cite

Background/Aim: The combination of atezolizumab plus bevacizumab (Atz/Bev) has become widely used as a firstline therapy for advanced hepatocellular carcinoma (HCC). However, for post-Atz/Bev therapy, evidence on the outcomes of molecular targeted agents, such as lenvatinib, is limited. The present study aimed to assess the clinical effectiveness of lenvatinib on advanced HCC in patients who had previously undergone Atz/Bev treatment. Patients and Methods: Twenty patients with HCC, who received lenvatinib after Atz/Bev treatment, were enrolled in the study. In particular, we examined the impact of adverse events (AEs), such as anorexia and general fatigue. During the treatment, lenvatinib dosages were adjusted or temporarily discontinued in response to AEs. Treatment outcomes were retrospectively evaluated. Results: The objective response rate (ORR) and disease control rate (DCR) for lenvatinib treatment were 25.0% and 95.0%, respectively, according to the Response Evaluation Criteria in Solid Tumors. The median progression-free survival (PFS) was 6.0 months, and the median overall survival (OS) was 10.5 months. Eleven patients experienced anorexia or fatigue, leading to a reduction in the dose of lenvatinib but not to a significant difference in the time to drug discontinuation. Importantly, there were no significant differences between the 11 anorexia/fatigue-suffering patients and the nine other patients with regard to PFS and OS. Conclusion: Lenvatinib can be efficacious and safe for treating advanced HCC patients previously treated with Atz/Bev, and AEs such as anorexia and general fatigue can be effectively managed without losing lenvatinib's therapeutic benefits.

show abstract

Clinical Outcomes of Cabozantinib in Patients Previously Treated with Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma—Importance of Good Liver Function and Good Performance Status

Cited by 7 publications

References 47 publications

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma

Clinical Outcomes With Lenvatinib in Patients Previously Treated With Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma

Contact Info

Product

Resources

About