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Korean Cancer Study Group 
Webzine Vol.37  SEP 2025 
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KCSG ์—ฐ๊ตฌ ๋…ผ๋ฌธ ์†Œ๊ฐœ
โ–ถ KCSG HN15-16
Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial

์ €๋„: Cancer Res Treat. 2025 Jan 31. Online ahead of print.

 

์ œ1์ €์ž ๊น€๊ทœํ˜„ (์„ธ๋ธŒ๋ž€์Šค๋ณ‘์›)

 

Q. ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ์€?

์žฌ๋ฐœ์„ฑ/์ „์ด์„ฑ ๋‘๊ฒฝ๋ถ€ ํŽธํ‰์„ธํฌ์•”(R/M HNSCC)์˜ 1์ฐจ ์น˜๋ฃŒ๋กœ ๋ฉด์—ญํ•ญ์•”์ œ์™€ ๋ฐฑ๊ธˆ๊ธฐ๋ฐ˜ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์ด ํ‘œ์ค€์น˜๋ฃŒ๋กœ ์‚ฌ์šฉ๋ฉ๋‹ˆ๋‹ค. ํ•˜์ง€๋งŒ, cetuximab ์™ธ์—๋Š” ํ‘œ์ ์น˜๋ฃŒ์ œ๊ฐ€ ํ™•๋ฆฝ๋˜์ง€ ์•Š์€ ์ƒํ™ฉ์ž…๋‹ˆ๋‹ค. NGS ๊ธฐ๋ฐ˜ ์ •๋ฐ€์˜๋ฃŒ ์ ‘๊ทผ๋ฒ•์„ ํ†ตํ•ด PIK3CA, CDKN2A, EGFR, CCNDA, FGFR ๋“ฑ ๋‹ค์–‘ํ•œ ๋ถ„์žํ‘œ์ ์ด ๋ฐœ๊ตด๋˜์—ˆ๊ณ , ์ด๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ๋‘๊ฒฝ๋ถ€์•”์—์„œ์˜ actionable target๊ณผ ํ‘œ์ ์น˜๋ฃŒ ๊ฐ€๋Šฅ์„ฑ์„ ํ™•์ธํ•˜๊ธฐ ์œ„ํ•˜์—ฌ ๋Œ€ํ•œํ•ญ์•”์š”๋ฒ•์—ฐ๊ตฌํšŒ(KCSG)๊ฐ€ ์ฃผ๊ด€ํ•œ TRIUMPH(KCSG-HN15-16) umbrella trial์ด ์ง„ํ–‰๋˜์—ˆ์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€?

TRIUMPH ์—ฐ๊ตฌ๋Š” ๋ฐฑ๊ธˆ๊ธฐ๋ฐ˜ ์น˜๋ฃŒ์— ์‹คํŒจํ•œ R/M HNSCC ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•˜๋Š” ๋‹ค๊ธฐ๊ด€, ๋‹ค์ฝ”ํ˜ธํŠธ ์ •๋ฐ€์˜๋ฃŒ ์ž„์ƒ์‹œํ—˜์ž…๋‹ˆ๋‹ค. ๋ณธ ๋…ผ๋ฌธ์€ TRIUMPH ์—ฐ๊ตฌ ๋‚ด์˜ 5๊ฐœ์˜ ์น˜๋ฃŒ๊ตฐ ์ค‘ alpelisib์— ๋Œ€ํ•œ in-depth report๋กœ, PI3K ๊ฒฝ๋กœ ๋ณ€์ด๊ฐ€ ์žˆ๋Š” ํ™˜์ž์—์„œ PI3Kฮฑ ์–ต์ œ์ œ alpelisib (BYL719) ๋‹จ๋…์š”๋ฒ•์˜ ์น˜๋ฃŒํšจ๊ณผ์™€ PIK3CA ๋ณ€์ด ๋ถ€์œ„๋ณ„ ๋ฐ˜์‘ ์ฐจ์ด๋ฅผ ์ƒ์„ธ ๋ถ„์„ํ–ˆ์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•?

์—ฐ๊ตฌ๋Š” ์‚ฌ์ „์— ์œ ์ „์ž ๋ถ„์„(NGS ๋ฐ RNA Nanostring assay)์„ ํ†ตํ•ด ํ™˜์ž์˜ ์ข…์–‘ ์œ ์ „์ž๋ฅผ ๋ถ„์„ํ•œ ๋’ค, ๋ถ„์ž์ข…์–‘์œ„์›ํšŒ(MTB) ์‹ฌ์˜๋ฅผ ๊ฑฐ์ณ ํ•ด๋‹น ์œ ์ „์ž ๋ณ€์ด์— ๋งž๋Š” ์น˜๋ฃŒ๊ตฐ์œผ๋กœ ๋ฐฐ์ •ํ–ˆ์Šต๋‹ˆ๋‹ค. PI3K ๊ฒฝ๋กœ ๋ณ€์ด๊ฐ€ ํ™•์ธ๋œ ํ™˜์ž๋“ค์€ alpelisib 350mg 1์ผ 1ํšŒ ๋‹จ๋…์š”๋ฒ•์„ ๋ฐ›์•˜๊ณ , ์น˜๋ฃŒ๋Š” ์งˆ๋ณ‘ ์ง„ํ–‰, ๋ถˆ๊ฐ€ํ”ผํ•œ ๋…์„ฑ, ๋˜๋Š” ํ™˜์ž ์ฒ ํšŒ ์‹œ๊นŒ์ง€ ์ง€์†๋˜์—ˆ์Šต๋‹ˆ๋‹ค. 1์ฐจ ํ‰๊ฐ€๋ณ€์ˆ˜๋Š” 8์ฃผ ์‹œ์ ์˜ ์งˆ๋ณ‘์กฐ์ ˆ๋ฅ (DCR)์ด์—ˆ์œผ๋ฉฐ, 2์ฐจ ๋ณ€์ˆ˜๋กœ๋Š” ๊ฐ๊ด€์  ๋ฐ˜์‘๋ฅ (ORR), ๋ฌด์ง„ํ–‰์ƒ์กด๊ธฐ๊ฐ„(PFS), ์ „์ฒด์ƒ์กด๊ธฐ๊ฐ„(OS), ์•ˆ์ •์„ฑ์ด ํฌํ•จ๋˜์—ˆ์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ?

์ด 203๋ช…์˜ ํ™˜์ž ์ค‘ 42๋ช…์ด alpelisib arm ์— ๋“ฑ๋ก๋˜์—ˆ์œผ๋ฉฐ, ์ด ์ค‘ 33๋ช…์ด ํšจ๋Šฅ ๋ถ„์„์— ํฌํ•จ๋˜์—ˆ์Šต๋‹ˆ๋‹ค. DCR์€ 65.6%๋กœ ์‚ฌ์ „๊ฐ€์„ค(DCR โ‰ฅ 50%)์„ ์ถฉ์กฑํ–ˆ์œผ๋ฉฐ, ORR์€ 21.2%, ์ค‘์•™ PFS๋Š” 3.4๊ฐœ์›”, OS๋Š” 12.4๊ฐœ์›”์ด์—ˆ์Šต๋‹ˆ๋‹ค. ํŠนํžˆ PIK3CA ๋Œ์—ฐ๋ณ€์ด ๋ถ€์œ„๋ณ„ ๋ถ„์„์—์„œ H1047 kinase domain ๋ณ€์ด๋ฅผ ๊ฐ€์ง„ ํ™˜์ž์—์„œ PFS๊ฐ€ 1.6๊ฐœ์›”๋กœ, helical domain ๋ณ€์ด(E542/E545)๋ฅผ ๊ฐ€์ง„ ํ™˜์ž์˜ 7.3๊ฐœ์›” ๋Œ€๋น„ ์œ ์˜ํ•˜๊ฒŒ ์งง๊ฒŒ ๋‚˜ํƒ€๋‚ฌ์Šต๋‹ˆ๋‹ค(p=0.017). OS ์—ญ์‹œ H1047 ๋ณ€์ด์—์„œ ์งง์€ ๊ฒฝํ–ฅ์„ ๋ณด์˜€์œผ๋‚˜ ํ†ต๊ณ„์  ์œ ์˜์„ฑ์—๋Š” ๋ฏธ์น˜์ง€ ๋ชปํ–ˆ์Šต๋‹ˆ๋‹ค(p=0.096). ์•ˆ์ •์„ฑ ๋ถ„์„์— ํฌํ•จ๋œ 42๋ช…์˜ ํ™˜์ž ์ค‘ ๊ฐ€์žฅ ํ”ํ•œ ์ด์ƒ๋ฐ˜์‘์€ ๊ณ ํ˜ˆ๋‹น(61.9%), ์‹์š•์ €ํ•˜(47.6%), ํ”ผ๋กœ(33.3%)์˜€์œผ๋ฉฐ, Grade 3 ์ด์ƒ์˜ ๊ณ ํ˜ˆ๋‹น์ด 45.2%์—์„œ ๋ณด๊ณ ๋˜์—ˆ์Šต๋‹ˆ๋‹ค. ๋Œ€๋ถ€๋ถ„์˜ ๋ถ€์ž‘์šฉ์€ ์šฉ๋Ÿ‰ ์กฐ์ ˆ๊ณผ ์ง€์ง€์  ์น˜๋ฃŒ๋กœ ๊ด€๋ฆฌ ๊ฐ€๋Šฅํ–ˆ์œผ๋ฉฐ, ์ƒˆ๋กœ์šด ๋…์„ฑ ์‹ ํ˜ธ๋Š” ๊ด€์ฐฐ๋˜์ง€ ์•Š์•˜์Šต๋‹ˆ๋‹ค.


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

TRIUMPH ์—ฐ๊ตฌ๋Š” ๋Œ€ํ•œํ•ญ์•”์š”๋ฒ•์—ฐ๊ตฌํšŒ(KCSG) ์ฃผ๊ด€์œผ๋กœ ๊ตญ๋‚ด 35๊ฐœ ๊ธฐ๊ด€์ด ์ฐธ์—ฌํ•ด, ๋‘๊ฒฝ๋ถ€์•”์—์„œ ์•”์œ ์ „์ž ๋ณ€์ด์— ๊ธฐ๋ฐ˜ํ•œ ์ •๋ฐ€์˜๋ฃŒ ์น˜๋ฃŒ์ „๋žต์˜ ๊ฐ€๋Šฅ์„ฑ์„ ์ œ์‹œํ•œ ๋Œ€๊ทœ๋ชจ ์ž„์ƒ์‹œํ—˜์ž…๋‹ˆ๋‹ค. ์ „์ฒด ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋Š” Journal of Clinical Oncology์— ๋ฐœํ‘œ๋˜์—ˆ์œผ๋ฉฐ, alpelisib์€ R/M HNSCC ํ™˜์ž์—์„œ PIK3CA ๋ณ€์ด ๋ถ€์œ„์— ๋”ฐ๋ผ ์ฐจ๋“ฑ์ ์ธ ์น˜๋ฃŒ ํšจ๊ณผ๋ฅผ ๋ณด์˜€์œผ๋ฉฐ, ํŠนํžˆ H1047 kinase domain ๋ณ€์ด๋ฅผ ๊ฐ€์ง„ ํ™˜์ž์—์„œ ๋ถˆ๋Ÿ‰ํ•œ ์˜ˆํ›„๋ฅผ ๋ณด์—ฌ, NGS ๊ธฐ๋ฐ˜ ๋งž์ถค์น˜๋ฃŒ ์ „๋žต์˜ ํ•„์š”์„ฑ๊ณผ ํ–ฅํ›„ ๋Œ€๊ทœ๋ชจ ๋ฌด์ž‘์œ„ ๋น„๊ต ๋ฐ ๋ณ‘์šฉ์š”๋ฒ• ์—ฐ๊ตฌ์˜ ์ค‘์š”์„ฑ์„ ์‹œ์‚ฌํ•ฉ๋‹ˆ๋‹ค. ์—ฐ๊ตฌ์— ์ฐธ์—ฌํ•ด ์ฃผ์‹  ์—ฌ๋Ÿฌ ๊ธฐ๊ด€์˜ ์—ฐ๊ตฌ์ž ๋ถ„๋“ค๊ณผ ํ™˜์ž ๋ฐ ๋ณดํ˜ธ์ž๋ถ„๋“ค๊ป˜ ๊ฐ์‚ฌ์˜ ๋ง์”€์„ ์ „ํ•ฉ๋‹ˆ๋‹ค.

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