Clinical trial에 등록하기 어려운 HCC 환자에서 사용되는 2차 약제는 다음과 같습니다.
① sorafenib (1차 약제로 사용하지 않은 경우)
② regorafenib
③ nivolumab with or without ipilimumab
④ pembrolizumab
⑤ lenvatinib (1차 약제로 사용하지 않은 경우)
소라페닙 사용에도 암이 진행하거나 소라페닙을 복용하기 어려운 대부분의 환자에서 regorafenib보다는 immune checkpoint inhibitors인 nivolumab with or without ipilimumab 또는 pembrolizumab을 제안합니다.
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While regorafenib has also been approved for this patient group, we now suggest treatment with immune checkpoint inhibitors, given the potential for a higher objective response rate (including some complete responders) and the more favorable side effect profile. The higher response rate may translate into a real life benefit for patients with large or symptomatic tumors and may represent a preferred option for these patients, although this has yet to be confirmed in actual practice. |
최근 소라페닙에 치료 실패한 advanced hepatocellular carcinoma (HCC) 환자의 2차 치료를 위해 nivolumab plus ipilimumab 병합 치료가 FDA에 승인되었습니다.
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What's New Nivolumab plus ipilimumab for advanced hepatocellular cancer previously treated with sorafenib (March 2020) The combination of nivolumab plus ipilimumab was recently approved by the US Food and Drug Administration (FDA) for treatment of patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. Regulatory approval was largely based on results of the phase I/II CheckMate 040 trial, in which nearly 150 sorafenib-treated patients with advanced HCC and no worse than Child-Pugh A cirrhosis were treated with three different schedules of combined therapy. In the three groups combined, objective and complete response rates were 31 and 5 percent, respectively, and median response duration was 17 months. The rate of grade 3 or 4 treatment-related adverse events was 37 percent, most commonly pruritus and rash. When immunotherapy is selected for treatment of advanced HCC in patients with an adequate performance status, we now generally prefer combined therapy over monotherapy with nivolumab or pembrolizumab. |
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On March 10, 2020, the Food and Drug Administration granted accelerated approval to the combination of nivolumab and ipilimumab (OPDIVO and YERVOY, Bristol-Myers Squibb Co.) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. Efficacy of the combination was investigated in Cohort 4 of CHECKMATE-040, (NCT01658878) a multicenter, multiple cohort, open-label trial conducted in patients with HCC who progressed on or were intolerant to sorafenib. A total of 49 patients received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every 3 weeks for four doses, followed by single-agent nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity. The main efficacy outcome measures were overall response rate and duration of response as determined by blinded independent central review (BICR) using RECIST v1.1. ORR was 33% (n=16; 95% CI: 20, 48), with 4 complete responses and 12 partial responses. Response duration ranged from 4.6 to 30.5+ months, with 31% of responses lasting at least 24 months. The most common adverse reactions (³20%) with nivolumab in combination with ipilimumab are: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness. For HCC, the recommended doses are nivolumab 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. |
REF. UpToDat 2020.09.08
FDA grants accelerated approval to nivolumab and ipilimumab combinatio
Hematology / Oncology Approvals
www.fda.gov
