Presentation (CTI)

OBJECTIVES: Colorectal cancer is one of the most frequently occurring cancers in both men and women. The RAS family of oncogenes, particularly the KRAS protein, are among the most frequently mutated protein families in cancers. KRAS mutation testing is indicated in adults with unresectable, metastatic colorectal cancer (mCRC). The non-mutant wild-type (WT) KRAS gene in mCRC is associated with both sensitivity and resistance to treatment with epidermal growth factors (EGFR) inhibitors. This study aimed to synthesise efficacy estimates of panitumumab plus standard chemotherapy as first-line (1L) treatment in WT mCRC.
METHODS: A systematic search of published literature was undertaken on 23 October 2024 in Embase, MEDLINE, and the Cochrane Library. Supplementary searches also took place, involving manual checking of conference proceedings and trial registries, and citation tracking. Randomised controlled trials (RCTs) investigating the efficacy of panitumumab plus irinotecan or oxaliplatin-based chemotherapy for 1L WT mCRC were included. Two reviewers independently screened the literature, extracted data, assessed methodological quality, and conducted GRADE. Retrieved data was assessed for feasibility and synthesised via meta-analysis in R (PROSPERO protocol registration: CRD42024607580).
RESULTS: Of the 739 articles identified, 14 were selected for inclusion in the review and meta-analysis. These covered two RCTs; both were judged to have a high risk of bias. The PRIME study (NCT00364013) compared panitumumab to FOLFOX4, whereas the comparator arm in the VOLFI trial (NCT01328171) was mFOLFOXIRI. Based on the meta-analysis, panitumumab is associated with a longer overall survival (HR 0.74; 95% CI: 0.05, 11.37), a higher ORR (RR 1.25; 95% CI: 1.06, 2.60) and no difference in PFS (HR 1.00, 95% CI: 0.15, 6.77), compared to chemotherapy. The overall certainty of evidence using GRADE was low.
CONCLUSIONS: The 1L addition of panitumumab to standard chemotherapy may be beneficial for individuals with WT mCRC based on a synthesis of published evidence.