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Your search keyword '"El-Khoueiry A.B."' showing total 3 results
Start Over Author "El-Khoueiry A.B." Topic nivolumab
3 results on '"El-Khoueiry A.B."'

1. Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040.

Author

El-Khoueiry, A.B., Trojan, J., Meyer, T., Yau, T., Melero, I., Kudo, M., Hsu, C., Kim, T.-Y., Choo, S.-P., Kang, Y.-K., Yeo, W., Chopra, A., Soleymani, S., Yao, J., Neely, J., Tschaika, M., Welling, T.H., and Sangro, B.

Subjects
*NIVOLUMAB, *ADVERSE health care events, *HEPATOCELLULAR carcinoma
Abstract

Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced groups of CheckMate 040 is presented here. Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator as per RECIST version 1.1 (dose expansion). Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 21%) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death-ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6 months) and 15.1 months (95% CI 13.0-18.2 months) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced groups; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% of patients in the sorafenib-naive and sorafenib-experienced groups, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC. • At 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit in patients with aHCC. • ORR was 20% in the sorafenib (SOR)-naive group and 14% in the SOR-experienced group. • 3-year OS rates were 28% in the SOR-naive and 20% in the SOR-experienced groups; 5-year rates were 14% and 12%, respectively. • The safety profile of nivolumab monotherapy was manageable and no new safety signals were identified. • Higher ORR and longer OS were noted with baseline PD-L1 ≥1% versus <1% and were more prominent in the SOR-experienced group. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib

Author

Tae-You Kim, Jennifer J. Knox, Ho Yeong Lim, Ignacio Melero, Yoon-Koo Kang, Masatoshi Kudo, Francesco Tovoli, Chiun Hsu, Thomas Yau, Jaclyn Neely, Aiwu Ruth He, Ming Mo Hou, Bruno Sangro, Yun Shen, Tami Wisniewski, Jeffrey Anderson, Ana Matilla, Armando Santoro, Bassel F. El-Rayes, Anthony B. El-Khoueiry, Mirelis Acosta-Rivera, Yau T., Kang Y.-K., Kim T.-Y., El-Khoueiry A.B., Santoro A., Sangro B., Melero I., Kudo M., Hou M.-M., Matilla A., Tovoli F., Knox J.J., Ruth He A., El-Rayes B.F., Acosta-Rivera M., Lim H.-Y., Neely J., Shen Y., Wisniewski T., Anderson J., and Hsu C.

Subjects
Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Randomization, Ipilimumab, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, ipilimumab, nivolumab, business.industry, Liver Neoplasms, Correction, hepatocellular carcinoma, Regimen, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, immunotherapy, Nivolumab, business, medicine.drug
Abstract

Importance Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy. Objective To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib. Design, Setting, and Participants CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C). Interventions Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C). Main Outcomes and Measures Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1). Results Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis). Conclusions and Relevance In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study. Trial Registration ClinicalTrials.gov Identifier:NCT01658878

Published
2020
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