FDA Approves Companion Diagnostic for Panitumumab in mCRC

• Panitumumab (Vectibix) was previously approved for patients with metastatic colorectal cancer (mCRC) in June 2017 in combination with folinic acid, fluorouracil, and oxaliplatin (FOLFOX).

• CRCdx is the first approved real-time PCR-based test to meet the biomarker identification requirement for panitumumab in the United States.

• CRCdx will be available immediately.

The FDA has granted approval to the CRCdx RAS Mutation Detection Kit to be used as a companion diagnostic for panitumumab for patients with mCRC.¹

The CRCdx®RAS mutation detection kit is a molecular, in vitro diagnostic tool which was designed to detect 35 variants of KRAS and NRAS exon 2, 3, and 4 somatic mutations in patients with CRC. Genomic DNA is extracted from formalin-fixed, paraffin-embedded CRC tissue samples using the agent, and the kit has high sensitivity and specificity which enables the fast identification of patients who do not have RAS mutations.

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

“We expect CRCdx to improve access to RAS testing at small and mid-size laboratories by simplifying the testing procedure while improving the turnaround time and lowering the diagnostic costs,” Matthew Minkovsky, chief executive officer of EntroGen, stated in a news release. “CRCdx is available immediately.”

In June 2017, the FDA approved panitumumab in combination with FOLFOX as a frontline treatment for patients with RAS wild-type metastatic CRC.²

In addition to the new approval and prior frontline approval, panitumumab is also indicated as monotherapy for the treatment of these patients, following prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. For the determination of RAS status, specifically exons 2, 3, and 4 of KRAS and NRAS), the FDA also approved a multigene, next-generation sequencing-based companion diagnostic.

The frontline approval of panitumumab plus FOLFOX was based on findings from the phase 3 PRIME (NCT00364013) study in which patients with KRAS wild-type mCRC who were previously untreated and in the metastatic setting were enrolled and treated with the combination (n = 325). Among those enrolled, the median progression-free survival (PFS) was 9.6 months (95% CI, 9.2-11.1) with the combination vs 8.0 months (95% CI, 7.5-9.3) in the 331 patients treated with FOLFOX alone (HR, 0.80; 95% CI, 0.66-0.97; P =.02).

Across all 1183 patients with broader KRAS wild-type mCRC, panitumumab plus FOLFOX showed a median overall survival of 23.8 months vs 19.4 months for FOLFOX alone (HR, 0.82, 95% CI, 0.70--0.98). In the combination arm vs FOLFOX alone arm, the overall response rates were 54% (95% CI, 48%-59%) vs 47% (95% CI, 41%-52%), respectively.

REFERENCES

1. EntroGen receives FDA approval for CRCdx® RAS mutation detection kit as companion diagnostic for Vectibix. News release. EntroGen. October 2, 2023. Accessed October 5, 2023. https://tinyurl.com/5x92pc85

2. FDA approves Vectibix (panitumumab) for use in wild-type RAS metastatic colorectal cancer. News release. Amgen. June 29, 2017. Accessed October 5, 2023. https://tinyurl.com/54kd9dam