FDA Approves RAS Mutation Detection Kit as Companion Diagnostic for Panitumumab in mCRC

The FDA has approved the CRCdx®RAS Mutation Detection Kit as a companion diagnostic for panitumumab (Vectibix) in the treatment of patients with metastatic colorectal cancer (mCRC), according to an announcement from EntroGen.¹

“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.”

The molecular, in vitro diagnostic tool is designed to detect 35 variants of KRAS and NRAS exon 2, 3, and 4 somatic mutations in patients with CRC via genomic DNA extracted from formalin-fixed, paraffin-embedded CRC tissue samples. The kit’s high sensitivity and specificity allow for fast identification of patients without RAS mutations, who are most likely to benefit from panitumumab.

In June 2017, the FDA approved panitumumab in combination with FOLFOX for the frontline treatment of patients with RAS wild-type metastatic CRC.² The EGFR inhibitor is also indicated as monotherapy for the treatment of patients with RAS wild-type mCRC following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.³

Notably, panitumumab is not indicated for the treatment of patients with RAS-mutated mCRC or patients in whom RAS mutation status is unknown.

Data from the phase 3 PRIME (NCT00364013) helped support the 2017 approval of frontline panitumumab plus FOLFOX. In patients with KRAS wild-type mCRC who were previously untreated in the metastatic setting, those given the combination (n = 325) experienced a median progression-free survival (PFS) of 9.6 months (95% CI, 9.2-11.1) compared with 8.0 months (95% CI, 7.5-9.3) for those given FOLFOX alone (n = 331; HR, 0.80; 95% CI, 0.66-0.97; P = .02). The overall response rates were 54% (95% CI, 48%-59%) and 47% (95% CI, 41%-52%) for the combination and FOLFOX alone, respectively.

An exploratory analysis showed that patients with KRAS wild-type CRC treated with panitumumab plus FOLFOX achieved a median overall survival (OS) of 23.8 months (95% CI, 20.0-27.7) vs 19.4 months (95% CI, 17.4-22.6) for those given FOLFOX alone (HR, 0.83; 95% CI, 0.70-0.98).

Data from PRIME demonstrated that patients with RAS-mutant mCRC treated with panitumumab plus FOLFOX (n = 272) experienced a median PFS of 7.3 months (95% CI, 6.3-7.9) compared with 8.7 months (95% CI, 7.6-9.4) for patients treated with FOLFOX alone (n = 276; HR, 1.31; 95% CI, 1.07-1.60). The median OS was 15.6 months (95% CI, 13.4-17.9) for those treated with the combination vs 19.2 months (95% CI, 16.7-21.8) for those given FOLFOX alone (HR, 1.25; 95% CI, 1.02-1.55).

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://entrogen.com/web3/entrogen-receives-fda-approval-for-crcdx-ras-mutation-detection-kit-as-companion-diagnostic-for-vectibix/
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://www.amgen.com/newsroom/press-releases/2017/06/fda-approves-vectibix-panitumumab-for-use-in-wildtype-ras-metastatic-colorectal-cancer
3. Vectibix. Prescribing information. Amgen; 2021. Accessed October 5, 2023. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/vectibix/vectibix_pi.ashx