Current status of therapy with CDK4/6 inhibitors for advanced cancer in Japan

Luyendijik et al. report that with improvements of approximately 10 months in progression-free survival and up to 14 months in overall survival reported in randomized clinical trials (RCTs), the 3 CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are seen as important breakthroughs in the treatment against metastatic breast cancer in the Netherlands.

Cyclin-dependent kinase-4/6 (CDK4/6) is a protein-serine kinase involved in the cell cycle. CDK4 and CDK6 are physiologic RB1 kinases that are inhibited by the p14(ARF), p16(INK4), and p18 CDK inhibitors. p16(INK4), p14(ARF) are also known as cyclin-dependent kinase inhibitor-2 (CDKN2A/B). Therefore, the CDKN2A/B gene encodes proteins that regulate 2 critical cell cycle regulatory pathways, the p53 (TP53) pathway and the RB1 pathway.

During the period from December 2019 to December 2022, treatment methods for a total of 2791 cases (Ncc oncopanel test: 743 cases, F1CDx test: 2048 cases) were examined in cancer genomic medicine at Japanese national universities. A total of 124 cases of advanced lung cancer, a total of 34 cases of advanced head and neck cancer, and a total of 14 cases of liposarcoma were studied in cancer genomic medicine in Japan. From the results of cancer genome gene testing, CDKN2A/B loss was detected in 14 cases of advanced lung cancers, 6 cases of advanced head and neck cancers, and 9 cases of liposarcoma. Therefore, the CDK4/6 inhibitors palbociclib or abemaciclib were recommended for these patients. Currently, patients with advanced tumors with CDKN2A/B loss are being treated with palbociclib or abemaciclib.

In the future, if the Ministry of Health, Labor and Welfare approves the treatment of advanced breast cancer with CDK4/6 inhibitors in Japan, it is believed that new treatment methods for advanced breast cancer will be actively recommended.

Human papillomavirus (HPV)-infected pharyngeal cancer responds slightly better to immune checkpoint inhibitors

We do not have potential conflicts of interest.

Doctor specializing in cancer care/Doctor specializing in emerging infectious diseases

JAMA Network Open Published on February 19, 2023, by Kyoto@takumaH