EGFR陰性大腸癌をどうするか？

セツキシマブのバイオマーカー

EGFRの発現強度は，セツキシマブの抗腫瘍効果と相関しないことがわかってきており，EGFR陰性大腸癌においても，セツキシマブの有効性が示されるようになった^1）2）。

一方，KRAS のmutasion症例では，セツキシマブが無効であることが，レトロスペクティブな解析ではあるがASCO2008のCRYSTAL試験^3），OPUS試験^4）などで示された（図１，２）。

図１ CRYSTAL： PFS according to KRAS status

図２ OPUS： PFS according to KRAS status

1. Lenz HJ，et al：Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan，oxaliplatin，and fluoropyrimidines．J Clin Oncol 24：4914〜21，2006．
   
   

   RESULTS: The response rates in 346 patients, as determined by the investigators and IRC, were 12.4% (95% CI, 9.1 to 16.4) and 11.6% (95% CI, 8.4 to 16.4). The median progression-free survival (PFS) and survival times were 1.4 months (95% CI, 1.4 to 2.1) and 6.6 months (95% CI, 5.6 to 7.6), respectively. An acneiform rash occurred in 82.9% of patients; grade 3 rash was observed in 4.9%. Response and survival related strongly to the severity of the rash. In contrast, clinical benefit did not relate to EGFR immunostaining. EGFR tyrosine kinase domain mutations were not identified, and EGFR gene copy number did not relate to response or PFS, but to survival (P = .03).

   CONCLUSION: Cetuximab is active and well tolerated in metastatic CRC refractory to irinotecan, oxaliplatin, and fluoropyrimidines. The severity of rash was related to efficacy. Neither EGFR kinase domain mutations nor EGFR gene amplification appear to be essential for response to cetuximab in this setting.

   
   
   
2. Meropol NJ：Epidermal growth factor receptor inhibitors in colorectal cancer：It’s time to get back on target．J Clin Oncol　23：1791 〜 3，2005．Epub Jan 27，2005
   
   　　　この論文はeditorialである
   
   
3. Van Custem E，et al：Randomized phase III study of irinotecan and 5-FU/FA with or without Cetuximab in the fi rst-line treatment of patients with metastatic colorectal cancer（mCRC）：The CRYSTAL Trial； ASCO Annual Meeting（Abstr 400），2007．
   
   
4. Bokemeyer C，et al：KRAS status and effi cacy of fi rst-line treatment of patients with metastatic colorectal cancer（mCRC）with FOLFOX with or without cetuximab ：The OPUS experience．ASCO Annual Meeting（Abstr 4000），2008．