演題抄録

FACO Symposium

開催概要
開催回
第53回・2015年・京都
 

Molecular-targeted Therapy for Liver Cancer: Where Are We Now?

演題番号 : FS2-6

[筆頭演者]
Kudo Masatoshi:1 

1:Department of Gastroenterology and Hepatology, Faculty of Medicine, Kinki University

 

After approval of sorafenib in 2009 in Japan, 3 first-line global clinical trials (Sunitinib, Brivanib, Linifanib), 4 second-line global clinical trials (Evelorimus, Brivanib, Ramucirumab, S1), 4 TACE combination trials (Sorafanib [Japan-Korea post TACE], Sorafenib [SPACE], Brivanib [BRISK-TA], Orantinib [Oriental]), 2 adjuvant setting trials (Sorafenib [STORM], Peretinoin [NIK-333]) have been conducted. As is well known, all of these 13 clinical trials failed to achieve their primary endpoints. The reason for these negative trials may be partly related to drug toxicity or study design. Currently, phase III 1st line study of Lenvatinib is ongoing, which inhibits VEGFR1-3, FGFR1-4, PDGFR, C-MET, RET and KIT. Also, phase III Peretinoin (NIK-333) trial is ongoing as an adjuvant setting after resection and ablation. Phase III second-line trials of Regorafanib is also ongoing.
Apart from these "all comes" trial, enrichment clinical trials based on biomarker selection are also under clinical trials, such as Tivantinib for high C-met expression HCCs, Refametinib for RAS mutation (phase II) and Ramucirumab for patients with high AFP value (> 400ng/ml).
The paradigm shift in liver cancer treatment may be expected by the immune checkpoint inhibitor, anti PD-1 or PDL-1 inhibitor. The results of phase I study of Nivolumab (PD-1 mAb) were presented at ASCO 2015 and it showed response rate is as high as 20 % with 2 CR cases and durable response of PR or SD cases.
In conclusion, after 6 years post Sorafenib approval, the results of promising agents such as Lenvatinib, Tivantinib, Ramucirumab and Peretinoin may change the treatment strategy in HCC. In addition, Immuno-oncology (Immune checkpoint inhibitors) may change the treatment paradigm of HCC drastically.

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