[胰臟癌] CONKO-007 trial

在最新的ASCO 2022 裡面, 關於不可切除胰臟癌(locally advanced pancreatic cancer)的治療又有新的結果, 就是所謂的CONKO-007 trial, 這裡藉由整理這篇筆記, 順便來複習一下胰臟癌的重點!

首先先來看下胰臟癌可否切除的分類, 這個在NCCN 裡面有一個整理得很好的表格, 這裡引用這個表格

可否切除	動脈	靜脈
可切除(Resectable)	腫瘤完全沒有碰到動脈 (CA, SMA, CHA)	1.腫瘤沒有接觸到SMV or PV2. ≤180° contact without vein contour irregularity
邊緣可切除(Borderline resectable)	Head/uncinate process: 1. 腫瘤有接觸到CHA但並沒有延伸到CA or hepatic artery bifurcation,可以安全完整的手術和重建 2. 腫瘤接觸到SMA ≤180°. 3. 腫瘤接觸到血管結構變異* Pancreatic body/tail: 1. 腫瘤接觸到CA ≤180°	1. 腫瘤接觸SMV or PV of >180°, contact of ≤180° with contour irregularity of the vein or thrombosis of the vein, 可以安全完整的手術和重建 2. 腫瘤接觸IVC
不可切除(Locally advanced)	Head/uncinate process: 1. 腫瘤接觸>180° SMA or CA. Pancreatic body/tail: 1. 腫瘤接觸>180° SMA or CA. 2. 腫瘤接觸CA且主動脈侵犯	不能重建SMV/PV 因為腫瘤侵犯或者是阻塞(can be due to tumor or bland thrombus).

CONKO-007

為 phase III RCT, 收案條件為non-resectable pancreatic cancer, 病人接受 induction chemotherapy (IC) for 3 months (3 cycles gemcitabine (Gem, 1000 mg/m2 d1, 8, 15, q4w) or FOLFIRINOX (6 cycles, q2w)).  在接受誘導性化療後, 如果沒有progression 的話, 分成兩組, CT for another 3 months or receiving CRT (cumulative dose of 50.4Gy, single dose 1.8Gy + Gem 300 mg/m2 weekly, followed by 1 cycle of Gem 1000 mg/m2 at d1, 8, 15). 

Primary endpoint 是 overall survival. 

結果為 Median progression-free survival (PFS) (HR 0.919, 95% CI 0.702-1.203, p=0.540) and OS (HR 0.964, 95% CI 0.760-1.225, p=0.766) did not differ significantly in both arms, whereas the PFS rate tended to be higher in the CRT arm after 2 years. 

OS rates for CRM- R0 surgery with 87.5. ± 0.05% (1y) and 67.2 ± 0.05% (2y) were significantly higher (p<0.01) than for CRM+ R0 surgery with 66.7 ± 0.15% (1y) and 41.2 ± 0.1% (2y) as well as for patients without or incomplete surgery with 68.5 ± 0.03% (1y) and 26.4 ± 0.03% (2y)

結論就是在打完ICT後的胰臟癌病人, 如果沒有progression的話, 之後做CT or CRT 在 OS 跟 PFS 上沒有差別. CRT 可以增加 R0 CRM - resection and pCR rate without significant change in R0 resection rate. Pts with R0 CRM - resections had a better prognosis compared to patients with either R0 CRM+ or incomplete or without surgery. 

LAP07

關於這個主題在之前有一篇類似的study, 就是LAP07, 也是相當有名, 以下就來細讀, 其發表於2016年的 JAMA. 

實驗設計為phase III RCT, 共收案449個 locally advanced pancreatic cancer病人, 隨機分派分兩階段做:

第一階段, 223 patients 接受 1000 mg/m2 weekly of gemcitabine alone, 219 patients 接受 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib.

第二階段, 如果打完化療後四個月還是progression-free, 136 patients 接受 2 months of the same chemotherapy, 133 去做 chemoradiotherapy (54 Gy plus capecitabine).

primary outcome: overall survival from the date of the first randomization. 

Secondary outcomes: the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects.

結果為: 

With a median follow-up of 36.7 months, 

Median OS: chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and CRT at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). 

Median OS:  223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). 

CRT was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea.

結論就是ICT 使用gemcitabine 或者是 gemcitabine plus erlotinib 對OS 沒有差別; CRT 或者是 CT alone 對OS 也沒有差別; 不過CRT 可以降低local progression (32% vs 46%, P = .03)

ref. 
1. NCCN
2. CONKO-007
3. LAP07