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Korean Cancer Study Group 
Webzine 2021 Vol.21
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KCSG ์—ฐ๊ตฌ ๋…ผ๋ฌธ ์†Œ๊ฐœ
โ–ถ KCSG HN18-12 
Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12  

Cancer Res Treat. 2020 Dec 7. doi: 10.4143/crt.2020.824. [Online ahead of print.]

 

์ œ1์ €์ž ์ด์œค๊ทœ (๊ฐ•๋ถ์‚ผ์„ฑ๋ณ‘์›)

 

Q. ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ์€?

์žฌ๋ฐœ์„ฑ ์ „์ด์„ฑ ๋‘๊ฒฝ๋ถ€ ํŽธํ‰์ƒํ”ผ์„ธํฌ์•”์€ 1์ฐจ์น˜๋ฃŒ๋กœ 5-FU์™€ ํ”Œ๋ž˜ํ‹ฐ๋„˜ ๋ณตํ•ฉํ•ญ์•”์น˜๋ฃŒ์— ์‹คํŒจํ•˜๋ฉด, ์„ ํƒํ•  ์ˆ˜ ์žˆ๋Š” ์น˜๋ฃŒ ๋ฐฉ๋ฒ•์ด ๋งŽ์ง€ ์•Š์€ ๋งค์šฐ ์˜ˆํ›„๊ฐ€ ๋‚˜์œ ์•”์ž…๋‹ˆ๋‹ค. ๊ฐ์ข… ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ (PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor)๋“ค์ด ๋‘๊ฒฝ๋ถ€ํŽธํ‰์ƒํ”ผ์•” ์ž„์ƒ์—ฐ๊ตฌ์—์„œ ์ผ๋ถ€ ๊ธ์ •์ ์ธ ์น˜๋ฃŒ ์„ฑ์ ์„ ๋ณด์—ฌ ์ฃผ์—ˆ์œผ๋‚˜ ๊ณผ์—ฐ ์‹ค์ œ ์ž„์ƒ์—์„œ๋Š” ์„ฑ์ ์ด ์–ด๋– ํ• ์ง€์— ๋Œ€ํ•œ ๊ถ๊ธˆ์ฆ์ด ์žˆ์—ˆ์Šต๋‹ˆ๋‹ค.    


Q. ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€?

๋ณธ ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด ํ”Œ๋ž˜ํ‹ฐ๋„˜์„ ํฌํ•จํ•œ ํ•ญ์•”์น˜๋ฃŒ์—๋„ ์ง„ํ–‰ํ•˜๋Š” ์žฌ๋ฐœ์„ฑ ๋˜๋Š” ์ „์ด์„ฑ ๋‘๊ฒฝ๋ถ€ ํŽธํ‰์ƒํ”ผ์„ธํฌ์•” ํ™˜์ž๋“ค์—๊ฒŒ ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ์˜ ํšจ๊ณผ๋ฅผ ์‹ค์ œ ์ž„์ƒ์—์„œ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ ํ™˜์ž์˜ ์˜ˆํ›„๊ณผ ๊ด€๋ จ์ด ์žˆ๋Š” ์ž„์ƒ์  ๋ฐ”์ด์˜ค๋งˆ์ปค๋ฅผ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•?

๋ณธ ์—ฐ๊ตฌ๋Š” ์ค‘์•™๋Œ€ํ•™๊ต ํ˜ˆ์•ก์ข…์–‘๋‚ด๊ณผ ํ™ฉ์ธ๊ทœ ๊ต์ˆ˜๋‹˜์˜ ์ด๊ด„ํ•˜์— ๊ตญ๋‚ด11๊ฐœ ๋ณ‘์›์—์„œ ์ด 125๋ช…์˜ ํ™˜์ž๊ฐ€ ๋“ฑ๋ก๋˜์–ด ํ›„ํ–ฅ์ ์œผ๋กœ ๋ถ„์„์„ ํ•˜์˜€์Šต๋‹ˆ๋‹ค. ์—ฐ๊ตฌ์˜ ์ฃผ๋ชฉ์ ๋Š” ๋ฐ˜์‘๋ฅ ์ด๋ฉฐ, ๋ถ€๋ชฉ์ ์€ ์ „์ฒด์ƒ์กด๊ธฐ๊ฐ„, ๋ฌด์ง„ํ–‰์ƒ์กด๊ธฐ๊ฐ„์ด์˜€์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ?

์ด 125๋ช…์˜ ๋“ฑ๋ก๋œ ํ™˜์ž ์ค‘ 58%๊ฐ€ PD-1 ์–ต์ œ์ œ ๋‹จ๋… ์š”๋ฒ•์„ ํˆฌ์—ฌ ๋ฐ›์•˜์œผ๋ฉฐ, PD-L1 ์–ต์ œ์ œ ๋‹จ๋… ์š”๋ฒ•์€ 19%, CTLA-4 ์–ต์ œ์ œ์™€์˜ ๋ณ‘ํ•ฉ์น˜๋ฃŒ๋Š” 22%๊ฐ€ ํˆฌ์—ฌ ๋ฐ›์•˜์Šต๋‹ˆ๋‹ค. ์ „์ฒด ๋ฐ˜์‘๋ฅ ์€ 15% ์˜€๊ณ , ๋ฌด์ง„ํ–‰์ƒ์กด๊ธฐ๊ฐ„์€ 2.7๊ฐœ์›”, ์ „์ฒด์ƒ์กด๊ธฐ๊ฐ„์€ 10.8๊ฐœ์›”์ด์˜€์Šต๋‹ˆ๋‹ค. ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ์˜ ๋ฐ˜์‘์„ ์˜ˆ์ธกํ•˜ ์ˆ˜ ์žˆ๋Š” ์ž„์ƒ์ ์ธ ์ง€ํ‘œ๋กœ๋Š” neutrophil-to-lymphocyte ratio (NLR) ์˜€๋Š”๋ฐ, NLR>4 ์ธ ๊ฒฝ์šฐ ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ์˜ ๋ฐ˜์‘์ด ์˜๋ฏธ์žˆ๊ฒŒ ๋–จ์–ด์ง€๋Š” ๊ฒƒ์œผ๋กœ ํ™•์ธ๋˜์—ˆ์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ ๋งŽ์€ ์—ฐ๊ตฌ์ž๋“ค์ด ๋Š๋ผ๋Š” ๊ฒƒ ์ฒ˜๋Ÿผ ์น˜๋ฃŒ๋‹น์‹œ ์•”์˜ ํฌ๊ธฐ (tumor burden)๊ฐ€ ํฐ ๊ฒฝ์šฐ ๋นˆ์‘ ์ง€์† ๊ธฐ๊ฐ„์ด ๊ธธ์ง€ ์•Š์•˜๊ณ , ์•”์˜ ํฌ๊ธฐ๊ฐ€ ํฌ๊ฑฐ๋‚˜, ํ™œ๋™๋ ฅ์ด ์ข‹์ง€ ์•Š๊ฑฐ๋‚˜, NLR>4 ์ธ ๊ฒฝ์šฐ ์ „์ฒด ์ƒ์กด๊ธฐ๊ฐ„๋„ ์งง์•˜์Šต๋‹ˆ๋‹ค. ์ด๋ฒˆ ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด ๋‘๊ฒฝ๋ถ€ํŽธํ‰์ƒํ”ผ์„ธํฌ์•”์˜ ์‹ค์ œ ์น˜๋ฃŒ ์‹œ์— ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ๊ฐ€ ๋ฌธํ—Œ์—์„œ ๋ณด๊ณ ํ•œ ๋น„์Šทํ•œ ๊ฒฐ๊ณผ๋ฅผ ๋ณด์—ฌ์คŒ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ ์‹ค์ œ ์ž„์ƒ์—์„œ ๋ฐ”๋กœ ํ™•์ธ ํ•  ์ˆ˜ ์žˆ๋Š” ์—ฌ๋Ÿฌ ์ž„์ƒ์  ์ง€ํ‘œ๋“ค์„ ์ฐพ์„ ์ˆ˜ ์žˆ์—ˆ๊ธฐ ๋•Œ๋ฌธ์—, ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ ์ฒ˜๋ฐฉ์„ ๊ฒฐ์ •ํ•˜๋Š”๋ฐ ์žˆ์–ด์„œ ํฐ ๋„์›€์„ ์ค„ ์ˆ˜ ์žˆ์„ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐํ•ฉ๋‹ˆ๋‹ค.


Q. ๋งˆ์ง€๋ง‰์œผ๋กœ ํ•˜๊ณ  ์‹ถ์€ ๋ง์€?

์—ฐ๊ตฌ๋ฅผ ๊ธฐํšํ•˜๊ณ , ๋งˆ๋ฌด๋ฆฌ๊นŒ์ง€ ์ด๋Œ์–ด์ฃผ์‹  ํ™ฉ์ธ๊ทœ ๊ต์ˆ˜๋‹˜๊ณผ ํ•ด๋‹น ์—ฐ๊ตฌ์— ์ ๊ทน์ ์œผ๋กœ ์ฐธ์—ฌํ•ด ์ฃผ์‹  ๊ธฐ๊ด€ ์—ฐ๊ตฌ์ž๋ถ„๋“ค๊ป˜ ๊ฐ์‚ฌ๋“œ๋ฆฝ๋‹ˆ๋‹ค. ํ›„ํ–ฅ์  ๋ถ„์„์ด์ง€๋งŒ, ์‹œ์˜์ ์ ˆํ•œ ์ฃผ์ œ ์„ ์ •๋ถ€ํ„ฐ, IRB ์‹ฌ์˜, ๋ฐ์ดํ„ฐ ์ˆ˜์ง‘, ๊ฒฐ๊ณผ ๋ถ„์„ ๋ฐ ๋…ผ๋ฌธ ์ž‘์„ฑ๊นŒ์ง€ ๋‘๊ฒฝ๋ถ€์‹๋„์•” ๋ถ„๊ณผ์˜ ๋งŽ์€ ๊ต์ˆ˜๋‹˜๋“ค๊ป˜์„œ ๊ด€์‹ฌ๊ณผ ๊ฒฉ๋ ค๋ฅผ ํ•ด์ฃผ์—ˆ๊ธฐ์— ๋งˆ๋ฌด๋ฆฌ๊ฐ€ ์ž˜ ๋˜์—ˆ๋‹ค๊ณ  ์ƒ๊ฐํ•ฉ๋‹ˆ๋‹ค. ๋์œผ๋กœ ์—ฐ๊ตฌ ์ฃผ์ œ, ํ†ต๊ณ„ ๋ถ„์„, ๋…ผ๋ฌธ ์ž‘์„ฑ ๋“ฑ ๋ชจ๋“  ๊ณผ์ •์— ๋„์›€์„ ์ฃผ์‹  ์žฅํ˜„ ๊ต์ˆ˜๋‹˜, ๊น€๋ฒ”์„ ๊ต์ˆ˜๋‹˜๊ป˜ ๊ฐ์‚ฌ๋“œ๋ฆฝ๋‹ˆ๋‹ค.