De-escalated outcomes, c'est la vie.

The phase 3 non-inferiority XELAVIRI trial randomized 421 patients with metastatic colorectal cancer to standard upfront irinotecan + 5FU (or capecitabine) + bevacizumab indefinitely versus 5FU (or capecitabine) + bev with irinotecan only upon progression. The primary endpoint was time from enrollment to failure on irinotecan (TTF). The thought was that the benefit from the addition of bev may allow for safe delay of extra toxicity seen with irinotecan. Turned out the KRAS/BRAF- wildtype cancers saw a significant benefit in TTF with standard upfront combo of all agents (12 vs 9 months), while KRAS- (9 vs 10) and especially BRAF- (5 vs 7) mutant tumors did bad no matter what. TBL: Benefits seen from our standard upfront multi-agent regimens for metastatic colon cancer are primarily driven by responses among KRAS/BRAF- wildtype tumors. | Modest, J Clin Oncol 2018