Axel Grothey

Axel Grothey is one of the most influential clinical investigators in colorectal cancer (CRC) systemic therapy, with over two decades of research that has fundamentally shaped the chemotherapy and targeted therapy landscape for metastatic CRC. Having spent significant portions of his career at the Mayo Clinic before transitioning to the West Cancer Center & Research Institute, he has led or co-led pivotal trials that established current treatment standards. Grothey's work has been central to establishing the triplet chemotherapy regimen FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, irinotecan) as an effective intensified approach for fit patients with metastatic CRC, particularly in combination with bevacizumab. His research demonstrated that intensified first-line chemotherapy combined with antiangiogenic agents can achieve response rates sufficient to convert unresectable liver metastases to resectable disease, offering a potentially curative approach for a subset of patients. He has made major contributions to understanding the determinants of anti-EGFR therapy (cetuximab and panitumumab) efficacy in mCRC. His research showed that RAS mutations (KRAS exon 2, 3, 4 and NRAS exon 2, 3, 4) are negative predictive biomarkers for anti-EGFR therapy, extending the original KRAS codon 12/13 biomarker and establishing the current all-RAS testing requirement for anti-EGFR agent selection. This work saved patients with RAS-mutant CRC from ineffective treatments and directed anti-EGFR therapy toward the RAS wild-type population in whom benefit is realized. Grothey also conducted pivotal work on regorafenib, an oral multikinase inhibitor, in refractory mCRC — leading the CORRECT trial that demonstrated overall survival benefit in heavily pretreated patients and established regorafenib as the first approved agent specifically for refractory mCRC. Beyond chemotherapy, his research has contributed to understanding the optimal sequencing of biologic agents in mCRC, the role of maintenance therapy, and the emerging utility of rechallenge with anti-EGFR antibodies in RAS wild-type patients who have progressed after prior anti-EGFR exposure (guided by ctDNA).

Axel Grothey 是结直肠癌全身治疗领域最具影响力的临床研究者之一，超过二十年的研究从根本上塑造了转移性CRC的化疗和靶向治疗格局。 他的工作确立了FOLFOXIRI三联化疗方案在转移性CRC的价值，推动了将不可切除的肝转移灶转化为可切除病变的策略。他的研究扩展了RAS突变作为抗EGFR治疗预测性生物标志物的范围（从KRAS codon 12/13扩展至全RAS检测），并领导了CORRECT试验，确立了regorafenib作为难治性mCRC的首个获批药物。