RAS Mutation Detection Kit Earns FDA Approval for Panitumumab in CRC

The FDA previously approved panitumumab plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) as a frontline treatment for patients with metastatic CRC harboring a RAS wild-type mutation in June 2017.

The FDA has granted approval to the CRCdx RAS Mutation Detection Kit as a companion diagnostic for identifying patients with colorectal cancer (CRC) who may benefit from targeted therapy with panitumumab (Vectibix), according to a news release from EntroGen, the developer of the test.¹

The CRCdx RAS Mutation Detection Kit is the first FDA-approved polymerase chain reaction (PCR)-based assay to meet all biomarker identification requirements for panitumumab. Developers designed the kit to precisely detect KRAS and NRAS exon 2, 3, and 4 somatic mutations in CRC, allowing practices to quickly identify those who may be suitable to receive panitumumab while avoiding potential additional treatment costs and adverse effects.

“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 at EntroGen, said in the press release.

The FDA previously approved panitumumab plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) as a frontline treatment for patients with metastatic CRC harboring a RAS wild-type mutation in June 2017.² Panitumumab also received approval as monotherapy in the same population for those with disease progression following prior chemotherapy containing fluoropyrimidine, oxaliplatin, and irinotecan. Supporting data for the full approval came from the phase 3 PRIME trial (NCT00364013) and the phase 3 ASPECTT trial (NCT01001377).

Investigators of the PRIME trial reported that panitumumab plus FOLFOX produced a median progression-free survival (PFS) of 9.6 months vs 8.0 months with FOLFOX alone in patients with KRAS wild-type tumors (HR, 0.80; 95% CI, 0.66-0.97; P = .02). Additionally, the median overall survival (OS) in each respective arm was 23.8 months vs 19.4 months (HR, 0.82; 95% CI, 0.70-0.98).

In the ASPECTT study, patients receiving panitumumab (n = 499) experienced a median OS of 10.4 months compared with 10.0 months among those treated with cetuximab (Erbitux; n = 499; HR, 0.97; 95% CI, 0.84-1.11). Investigators highlighted that these data met the primary end point of noninferior OS in patients treated with panitumumab.

“Panitumumab has demonstrated a significant [OS] benefit to patients whose [metastatic] CRC does not have mutations in RAS, providing physicians with a novel targeted treatment option and allowing us to develop a personalized approach as we help patients [with] this devastating disease,” Marwan G. Fakih, MD, co-director of the Gastrointestinal Cancer Program at City of Hope in Duarte, California, said in a news release at the time of the approval.²

In the open-label, randomized PRIME study, patients with untreated metastatic CRC were randomly assigned to receive FOLFOX on days 1 and 2 with or without 6 mg/kg of panitumumab on day 1 of each 14-day cycle. The study’s primary end point was PFS, with secondary end points including OS, time to progression, and duration of response (DOR).

In the multicenter, open-label ASPECTT study, patients with EGFR-expressing KRAS wild-type metastatic CRC were randomly assigned to receive 400 mg/m² of cetuximab followed by 250 mg/m² intravenously every 7 days or 6 mg/kg of cetuximab intravenously every 2 weeks. The study’s secondary end points included objective response rate, time to response, DOR, and time to treatment failure.

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 18, 2023. https://shorturl.at/GSV24
2. FDA approves Vectibix® (Panitumumab) for use in wild-type RAS metastatic colorectal cancer. News release. Amgen. June 29, 2017. Accessed October 18, 2023. https://shorturl.at/gtCT0