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Korean Cancer Study Group 
Webzine Vol.31  MAR 2024 
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KCSG ์—ฐ๊ตฌ ๋…ผ๋ฌธ ์†Œ๊ฐœ
โ–ถ KCSG GU18-18 
Phase II study of a trastuzumab biosimilar in combination with paclitaxel for HER2-positive recurrent or metastatic urothelial carcinoma: KCSG GU18-18

์ €๋„: ESMO Open. 2023 Jun 27;8(4):101588. Online ahead of print.

 

์ œ1์ €์ž ๊น€๋ฏธ์†Œ (์„œ์šธ๋Œ€๋ณ‘์›) 

 

Q. ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ์€?

HER2 (ERBB2)๋Š” ์—ฌ๋Ÿฌ ์•”์ข…์—์„œ ์˜ค๋žซ๋™์•ˆ ์—ฐ๊ตฌ๋˜์–ด ์˜จ oncogene์œผ๋กœ, ๋ฌธํ—Œ์— ๋”ฐ๋ผ ์•ฝ 10% ์ •๋„์˜ ์š”๋กœ์ƒํ”ผ์•”์—์„œ HER2 amplification์ด ๋ณด๊ณ ๋˜๋ฉฐ, HER2 overexpression์€ 0~25% ๋ฒ”์œ„๋กœ ๋‹ค์–‘ํ•˜๊ฒŒ ๋ณด๊ณ ๋˜๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๋ ‡๊ฒŒ HER2 aberration์ด ์š”๋กœ์ƒํ”ผ์•”์—์„œ ๋น„๊ต์  ํ”ํ•˜๊ฒŒ ๊ด€์ฐฐ๋จ์— ๋”ฐ๋ผ HER2-directed therapy์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๋“ค์ด ์‹œ๋„๋˜์–ด ์™”์œผ๋‚˜ ์ผ๊ด€๋œ ๊ฒฐ๊ณผ๋ฅผ ๋ณด์—ฌ์ฃผ์ง€๋Š” ๋ชปํ•˜์˜€์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€?

๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ๋ฐฑ๊ธˆ๊ธฐ๋ฐ˜ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ์‹คํŒจํ•œ HER2 ์–‘์„ฑ ์žฌ๋ฐœ์„ฑ ํ˜น์€ ์ „์ด์„ฑ ์š”๋กœ์ƒํ”ผ์•” ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ paclitaxel๊ณผ trastuzumab์˜ biosimilar์ธ trastuzumab-pkrb ๋ณ‘ํ•ฉ์š”๋ฒ•์˜ ์œ ํšจ์„ฑ๊ณผ ์•ˆ์ „์„ฑ์„ ํ‰๊ฐ€ํ•˜๊ณ ์ž ํ•˜์˜€์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•?

๊ตญ๋‚ด 10๊ฐœ ๊ธฐ๊ด€์ด ์ฐธ์—ฌํ•œ ๋‹ค๊ธฐ๊ด€ 2์ƒ ์ž„์ƒ์‹œํ—˜์œผ๋กœ ์ง„ํ–‰๋˜์—ˆ๊ณ , ์—ฐ๊ตฌ์˜ 1์ฐจ ๋ชฉ์ ์€ ๊ฐ๊ด€์  ๋ฐ˜์‘๋ฅ  (ORR) ์ด์—ˆ์œผ๋ฉฐ, 2์ฐจ ๋ชฉ์ ์œผ๋กœ ์ „์ฒด ์ƒ์กด (OS), ๋ฌด์ง„ํ–‰ ์ƒ์กด๊ธฐ๊ฐ„ (PFS), ์•ˆ์ „์„ฑ (safety)์„ ํ™•์ธํ•˜์˜€์Šต๋‹ˆ๋‹ค. ๋ชจ๋“  ํ™˜์ž๋“ค์€ 3์ฃผ๋งˆ๋‹ค trastuzumab-pkrb (8 mg/kg loading ์ดํ›„ 3์ฃผ๋งˆ๋‹ค 6 mg/kg)๊ณผ paclitaxel (175 mg/m2)์„ ํˆฌ์—ฌ๋ฐ›์•˜๊ณ , ๋ณ‘์šฉ์š”๋ฒ• 6์ฃผ๊ธฐ ์ดํ›„ ์งˆ๋ณ‘ ์ง„ํ–‰์ด๋‚˜ ๊ฒฌ๋””๊ธฐ ์–ด๋ ค์šด ์ด์ƒ๋ฐ˜์‘์ด ๋ฐœ์ƒํ•˜์ง€ ์•Š์„ ๊ฒฝ์šฐ ์ตœ๋Œ€ 2๋…„๊นŒ์ง€ trastuzumab-pkrb ์œ ์ง€์น˜๋ฃŒ๋ฅผ ๋ฐ›์•˜์Šต๋‹ˆ๋‹ค. HER2 ์–‘์„ฑ์€ 2013 ASCO/CAP HER2 testing guideline์— ๋”ฐ๋ผ immunohistochemistry (IHC) ๋ฐฉ๋ฒ•์œผ๋กœ ํ‰๊ฐ€ํ•˜์˜€์Šต๋‹ˆ๋‹ค.


Q. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ?

2019๋…„ 4์›”๋ถ€ํ„ฐ 2020๋…„ 12์›”๊นŒ์ง€ ์ด 27๋ช…์˜ ํ™˜์ž๊ฐ€ ๋“ฑ๋ก๋˜์—ˆ๊ณ  ์›๋ฐœ ๋ถ€์œ„๋Š” ๋ฐฉ๊ด‘ (59.3%)์ด ๊ฐ€์žฅ ํ”ํ•˜์˜€๊ณ , ๋‹ค์Œ์œผ๋กœ ์š”๊ด€ (22.2%), ์‹ ์šฐ (14.8%), ์š”๋„ (7.4%) ์˜€์Šต๋‹ˆ๋‹ค. ์ด์ „ ์น˜๋ฃŒ๋ ฅ์œผ๋กœ ๋ชจ๋“  ํ™˜์ž๊ฐ€ gemcitabine๊ณผ cisplatin ํ˜น์€ carboplatin์„ ํˆฌ์•ฝ ๋ฐ›์•˜์œผ๋ฉฐ, 74%์˜ ํ™˜์ž๊ฐ€ ๋ฉด์—ญ๊ด€๋ฌธ์–ต์ œ์ œ๋ฅผ ํˆฌ์•ฝ๋ฐ›์•˜์Šต๋‹ˆ๋‹ค. ํ‰๊ฐ€ ๊ฐ€๋Šฅํ•œ 26๋ช…์˜ ํ™˜์ž ์ค‘ 1๋ช…์˜ ํ™˜์ž์—์„œ ์™„์ „๋ฐ˜์‘ (CR), 12๋ช…์˜ ํ™˜์ž์—์„œ ๋ถ€๋ถ„๋ฐ˜์‘ (PR)์„ ๋ณด์—ฌ ORR์€ 48.1% ์˜€์Šต๋‹ˆ๋‹ค. Median PFS๋Š” 8.4๊ฐœ์›” (95% CI 6.2-8.8, median OS๋Š” 13.5๊ฐœ์›” (95% CI 9.8-NR) ์ด์—ˆ์Šต๋‹ˆ๋‹ค.




์น˜๋ฃŒ์™€ ์—ฐ๊ด€๋œ ์ด์ƒ๋ฐ˜์‘ ์ค‘ ๋ง์ดˆ์‹ ๊ฒฝ๋ณ‘์ฆ (88.9%)์ด ๊ฐ€์žฅ ํ”ํ•˜๊ฒŒ ๋ณด๊ณ ๋˜์—ˆ๊ณ , 3๋“ฑ๊ธ‰ ์ด์ƒ์˜ ์ด์ƒ๋ฐ˜์‘์€ ํ˜ธ์ค‘๊ตฌ ๊ฐ์†Œ (25.9%), ํ˜ˆ์†ŒํŒ ๊ฐ์†Œ (7.4%) ๋ฐ ๋นˆํ˜ˆ (7.4%) ์ด์—ˆ์Šต๋‹ˆ๋‹ค.


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

๋ณธ ์—ฐ๊ตฌ์˜ ORR์€ 48.1%๋กœ primary endpoint (ORR 55%)๋ฅผ ๋งŒ์กฑํ•˜์ง€ ๋ชปํ•˜์˜€์Šต๋‹ˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋ฉด์—ญํ•ญ์•”์ œ์— ์‹คํŒจํ•œ ํ™˜์ž๋“ค์ด ๋‹ค์ˆ˜ ํฌํ•จ๋˜์—ˆ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ์ด์ „ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋“ค์— ๋น„ํ•˜์—ฌ ๋น„๊ต์  ๋†’์€ ๋ฐ˜์‘๋ฅ ์„ ๋ณด์˜€๊ณ , ์น˜๋ฃŒ ๋ฐ˜์‘์ด ์žฅ๊ธฐ๊ฐ„ ์œ ์ง€๋˜๋Š” ํ™˜์ž๋“ค์ด ๊ด€์ฐฐ๋˜์–ด ์š”๋กœ์ƒํ”ผ์•”์—์„œ HER2-directed therapy์˜ ์ ์šฉ ๊ฐ€๋Šฅ์„ฑ์„ ๋ณด์—ฌ์ฃผ์—ˆ์Šต๋‹ˆ๋‹ค. ๋‹ค๋งŒ, ์š”๋กœ์ƒํ”ผ์•”์—์„œ HER2 ์–‘์„ฑ์— ๋Œ€ํ•œ ๊ธฐ์ค€์ด ๋ช…ํ™•ํžˆ ์ •๋ฆฝ๋˜์–ด ์žˆ์ง€ ์•Š๊ณ , HER2 IHC ํŒ๋…์— ๋Œ€ํ•œ interobserver variability ๋“ฑ์„ ๊ณ ๋ คํ•˜์—ฌ HER2-directed therapy์— ์ด๋“์„ ๋ณผ ์ˆ˜ ์žˆ๋Š” ํ™˜์ž๋ฅผ ์ ์ ˆํžˆ ์„ ๋ณ„ํ•ด๋‚ด๋Š” ๊ฒƒ์ด ์ค‘์š”ํ•˜๋‹ค๊ณ  ์ƒ๊ฐํ•˜์˜€์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ ์ตœ๊ทผ ์š”๋กœ์ƒํ”ผ์•”์—์„œ ์—ฌ๋Ÿฌ HER2-targeting antibody-drug conjugate ๋“ค์ด ์—ฐ๊ตฌ๋˜๊ณ  ์žˆ์–ด ๊ทธ ๊ฒฐ๊ณผ๋ฅผ ๊ธฐ๋Œ€ํ•ด๋ด๋„ ์ข‹์„ ๊ฒƒ ๊ฐ™์Šต๋‹ˆ๋‹ค. ๋งˆ์ง€๋ง‰์œผ๋กœ, ๋ณธ ์—ฐ๊ตฌ์— ์ฐธ์—ฌํ•˜์‹  ํ™˜์ž๋ถ„๋“ค๊ณผ ๊ฐ€์กฑ๋“ค, ๊ทธ๋ฆฌ๊ณ  ๋งŽ์€ ๋…ธ๋ ฅ๊ณผ ๋„์›€์„ ์ฃผ์‹  KCSG ์‚ฐํ•˜ ์—ฌ๋Ÿฌ ๊ธฐ๊ด€์˜ ๋™๋ฃŒ ์„ ์ƒ๋‹˜๋“ค, KCSG ๋ฐ์ดํ„ฐ์„ผํ„ฐ ๋‹ด๋‹น์ž๋‹˜๋“ค๊ป˜๋„ ํฐ ๊ฐ์‚ฌ์˜ ๋งˆ์Œ์„ ํ‘œํ•ฉ๋‹ˆ๋‹ค.