scholarly journals Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Ho Yeong Lim ◽  
Ann-Lii Cheng ◽  
Yee Chao ◽  
Thomas Yau ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
The Philippines ◽  
Advanced Hepatocellular Carcinoma ◽  
Asian Patients ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Grade 3

<b><i>Introduction:</i></b> KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. <b><i>Methods:</i></b> Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. <b><i>Results:</i></b> The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. <b><i>Conclusion:</i></b> Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: A retrospective, single-institution study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 339-339
Author(s):  
S. Lee ◽  
S. Yoon ◽  
S. Shin ◽  
H. Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Chemotherapy Group ◽  
Sorafenib Group ◽  
The Difference ◽  
Grade 3 ◽  
Novel Target

339 Background: Prior to the sorafenib era, most of the advanced hepatocellular carcinoma (HCC) patients had to rely only on conventional cytotoxic chemotherapy. But the introduction of sorafenib in 2008 had given HCC patients additional option for their treatment. However, given that sorafenib has been a nonreimbursable drug under the Korea public health system, most of treatment strategy has largely been determined by patients' affordability of the drug rather than by difference in efficacy and toxicity of the two treatments. Therefore, we compared the efficacy and toxicity of the two treatments by observing HCC patients. Methods: From January 2002 to December 2009, 173 patients with unresectable HCC had been retrospectively analyzed. Among them, 44 (25.4%) had been treated with sorafenib and the remaining had received cytotoxic chemotherapy. We evaluated objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: The median OS of sorafenib group was 23.0 weeks (95% CI, 8.1-37.9) vs. 43.6 weeks (95% CI, 34.0-37.9) for cytotoxic chemotherapy group. The median PFS for sorafenib group was 11.1 weeks (95% CI, 6.5-15.8) versus 12.4 weeks (95% CI, 8.1-16.7) for cytotoxic chemotherapy group. However, the difference in both findings had not been statistically significant (p=0.105 and p=0.496, respectively). ORR and DCR for sorafenib group were 2.3% and 52.3% versus 6.2% and 43.4% for cytotoxic chemotherapy group, respectively. Patients treated with chemotherapy had shown higher frequencies of grade 3 or 4 neutropenia, 19.7%, (vs. 0% for sorafenib). However, the group with sorafenib had reported a higher rate of all grade dermatologic toxicities such as hand-foot skin reaction, rash and pruritus. Conclusions: Our analysis indicates that efficacy of conventional chemotherapy is not inferior to that of sorafenib. Further research including novel target agent and cytotoxic chemotherapy is needed to improve clinical outcomes for advanced HCC. No significant financial relationships to disclose.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Aiwu Ruth He ◽  
Thomas Yau ◽  
Chiun Hsu ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Subgroup Analyses ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.

Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

2015 ◽  
Vol 33 (6) ◽  
pp. 728-734 ◽  
Author(s):  
Tadaaki Arizumi ◽  
Kazuomi Ueshima ◽  
Mina Iwanishi ◽  
Hirokazu Chishina ◽  
Masashi Kono ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Response ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
University Hospital ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Grade 3

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

2006 ◽  
Vol 24 (12) ◽  
pp. 1898-1903 ◽  
Author(s):  
Andrew X. Zhu ◽  
Lawrence S. Blaszkowsky ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
Alona Muzikansky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Vascular Tumor ◽  
Advanced Hepatocellular Carcinoma ◽  
Close Monitoring ◽  
Grade 3 ◽  
Transient Elevation

Purpose Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and Methods Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16. Results Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. Conclusion GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.

scholarly journals Phase 1b/2 trial of tepotinib in sorafenibpretreated advanced hepatocellular carcinoma with MET overexpression

2021 ◽  
Author(s):  
Thomas Decaens ◽  
Carlo Barone ◽  
Eric Assenat ◽  
Martin Wermke ◽  
Angelica Fasolo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 2 ◽  
Once Daily ◽  
Exact Test ◽  
Primary Endpoints ◽  
Phase 1B ◽  
Risk Balance ◽  
Grade 3

Abstract Background This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenibpretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b (‘3 + 3’ design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2). Results In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5–74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%). Conclusions Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit–risk balance in sorafenibpretreated aHCC with MET overexpression. Trial Registration ClinicalTrials.gov: NCT02115373.

scholarly journals Safety of PD-1/PD-L1 Inhibitors Combined With Palliative Radiotherapy and Anti-Angiogenic Therapy in Advanced Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Liting Zhong ◽  
Dehua Wu ◽  
Weiwei Peng ◽  
Hailong Sheng ◽  
Yazhi Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Advanced Hepatocellular Carcinoma ◽  
Patient Death ◽  
Angiogenic Therapy ◽  
Grade 3

BackgroundPrevious studies have explored cancer immunotherapy with radiotherapy or anti-angiogenic therapy, but no trials have reported a triple therapy approach. This study aimed to investigate safety and clinical outcome of PD-1/PD-L1 inhibitors combined with palliative radiotherapy and targeted angiogenesis therapy in hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C.MethodsConsecutive patients (n=16) treated with PD-1/PD-L1 inhibitors combined with radiotherapy and anti-angiogenic therapy in a bi-institutional cohort between July 2017 and December 2020 were retrospectively included. Radiotherapy was conducted within 14 days of the first administration of immunotherapy. The primary endpoint was treatment-related adverse event (TRAE).ResultsThe median follow-up was 383 days. Fifteen patients (93.8%) experienced at least 1 TRAE. The most common TRAEs of any grade were rash (25%), diarrhea (25%), aspartate aminotransferase increase (18.8%), alanine transaminase increase (18.8%), decreased appetite (18.8%), and fatigue (18.8%). Grade 3/4 TRAEs occurred in 4 patients (25%) and finally led to treatment interruption. No patient death was attributed to treatment. No specific events were responsible for the addition of radiotherapy. Six patients showed partial response, 7 showed stable disease, and 2 showed progressive disease. The objective response rate and disease control rate were 40.0% (95% CI 16.3%–67.7%) and 86.7% (95% CI 59.5%–98.3%), respectively. Moreover, the median progression-free survival was 140 days. Patients had a median overall survival of 637 days, and the estimated rates of survival at 6 and 12 months were 92.3% and 75.5%, respectively.ConclusionPD-1/PD-L1 inhibitors combined with palliative radiotherapy and anti-angiogenic therapy appear to be safe, with no unexpected adverse events. Additional studies exploring the clinical benefit are warranted.

Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 478-478 ◽  
Author(s):  
Thomas Yau ◽  
Vittorina Zagonel ◽  
Armando Santoro ◽  
Mirelis Acosta-Rivera ◽  
Su Pin Choo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Primary Endpoints ◽  
Tolerability Data ◽  
Grade 3

478 Background: The programmed death-1 inhibitor NIVO had durable responses and a manageable safety profile in pts with aHCC in CheckMate 040 (NCT01658878; El-Khoueiry et al. Lancet 2017) and is approved in the United States, Canada, Australia, and elsewhere for sorafenib (SOR)-treated pts with aHCC. In another CheckMate 040 cohort, NIVO + IPI combination therapy had durable responses in SOR-treated pts with aHCC, with objective response rates (ORRs) > 30% in each dosing arm (Yau et al. J Clin Oncol 2019). CABO is also approved for SOR-treated pts with aHCC; a pivotal phase 3 trial reported median overall survival (OS) of 10.2 mo (Abou-Alfa et al. N Engl J Med 2018). This is the first report of efficacy and safety of NIVO + CABO +/- IPI (doublet and triplet) combinations in pts with aHCC. Methods: SOR-naive or -experienced pts with aHCC were randomized to 2 arms: [1] NIVO 240 mg Q2W + CABO 40 mg daily or [2] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W + CABO 40 mg daily. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included ORR (investigator assessed using RECIST v1.1) and safety/tolerability. Data cutoff was January 2019. Results: 71 pts were randomized to NIVO + CABO (n = 36) or NIVO + IPI + CABO (n = 35). Investigator-assessed ORR was 17% (6 pts with partial response [PR]) in the NIVO + CABO arm and 26% (9 pts with PR) in the NIVO + IPI + CABO arm. Disease control rate was 81% for the NIVO + CABO arm and 83% for the NIVO + IPI + CABO arm; median progression-free survival was 5.5 mo for the NIVO + CABO arm and 6.8 mo for the NIVO + IPI + CABO arm. Median OS was not reached in either arm. Grade 3-4 treatment-related adverse events (TRAEs) were reported in 15 pts (42%) in the NIVO + CABO arm and 25 pts (71%) in the NIVO + IPI + CABO arm and led to discontinuation in 1 (3%) and 7 (20%) pts, respectively. No new safety signals were observed in either arm. Updated data describing the efficacy and safety of the combinations will be shown. Conclusions: In pts with aHCC, NIVO + CABO +/- IPI combination therapy led to clinically meaningful responses. Although the triplet had a higher rate of TRAEs observed than the doublet regimen, the majority of AEs were manageable and reversible. Clinical trial information: NCT01658878.

scholarly journals Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression

2021 ◽  
Author(s):  
Baek-Yeol Ryoo ◽  
Ann-Li Cheng ◽  
Zhenggang Ren ◽  
Tae-You Kim ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Primary Endpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 2 ◽  
Open Label ◽  
Asian Patients ◽  
Open Label Phase ◽  
Phase 1B

Abstract Background This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). Results In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26–0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. Conclusions Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. Trial registration ClinicalTrials.gov NCT01988493.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
Thomas Yau ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
Anthony B. El-Khoueiry ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4012 Background: NIVO monotherapy (mono) is approved for sorafenib (SOR)-treated pts with HCC based on data from CheckMate 040 (NCT01658878), which reported an objective response rate (ORR) of 14% and median overall survival (mOS) of 16 months (mo). This is the first report of efficacy and safety of the NIVO + IPI combination in SOR-treated pts with aHCC. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety and tolerability. Secondary endpoints included ORR (BICR per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS. Cutoff was 25 Sep 2018. Results: 148 SOR-treated pts were randomized. Minimum follow-up for OS from last pt randomization date to data cutoff was 24 mo. At baseline: 88% had vascular invasion or extrahepatic spread, 91% had BCLC stage C, 84% discontinued SOR due to disease progression and 14% due to toxicity. Overall, ORR was 31% (7 had a complete response [CR]) with a median DOR of 17 mo; DCR was 49% and 24-mo OS rate was 40%. Pts in arm A had a mOS of 23 mo and 4 pts had a CR. The table shows additional efficacy results by arm. Overall, NIVO + IPI was well tolerated; 37% of pts had a grade 3–4 treatment-related adverse event (TRAE; most common: pruritus and rash); 5% had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + IPI led to clinically meaningful responses and had an acceptable safety profile in SOR-treated pts, with an ORR twice that of NIVO mono (31% and 14%, respectively). Pts in arm A had the most promising mOS of 23 mo. Clinical trial information: NCT01658878. [Table: see text]

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