DEEPER Trial Final Analysis: m-FOLFOXIRI, Cetuximab Boosts PFS, OS in mCRC

A final analysis of the DEEPER trial presented at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium has demonstrated the benefits of m-FOLFOXIRI in combination with cetuximab for patients with RAS wild-type and left-sided metastatic colorectal cancer (mCRC).

In the DEEPER trial, researchers analyzed the use of m-FOLFOXIRI (irinotecan 150 mg/m², oxaliplatin 85 mg/m², 5-fluorouracil 2400 mg/m²) plus cetuximab in comparison with bevacizumab as initial therapy to determine the primary endpoint of depth of response (DpR). Previously presented results of the trial showed favorable progression-free survival (PFS) rates for patients with RAS/BRAF wild-type and left-sided tumors in the m-FOLFOXIRI and cetuximab arm.

Because the trial had a small number of overall survival (OS) events, the observation period was extended, with the final analysis performed at the cutoff date of August 2024.

The per-protocol set (PPS) involved a pre-planned survival analysis, which included patients evaluable for DpR. Outcomes were measured based on primary tumor sidedness, liver metastasis status, and BRAF status by using a log-rank test. Each statistical test was two-sided, and P values less than or equal to .05 were considered significant.

Of 359 patients enrolled in the trial, 321 were identified as belonging in the PPS. In patients with RAS wild-type and left-sided tumors, the median PFS and OS rates in the cetuximab versus bevacizumab arms were 13.9 months versus 12.1 months (hazard ratio [HR], 0.81; 95% CI, 0.63-1.05) and 45.3 months versus 41.9 months (HR, 0.85; 95% CI, 0.64-1.12), respectively.

In the PPS, BRAF status was available for 234 of 321 (73%) patients. Results of an exploratory analysis showed that PFS was significantly better in the cetuximab arm in 178 patients with RAS/BRAF wild-type and left-sided tumors than in those who received bevacizumab (median, 14.8 months vs 11.9 months; HR, 0.71; 95% CI, 0.52-0.97). The OS rate of the cetuximab and bevacizumab arms was 50.2 months and 40.2 months (HR, 0.74; 95% CI, 0.53-1.05), respectively.

According to liver disease status, m-FOLFOXIRI was linked to longer PFS and OS in patients with RAS/BRAF wild-type and left-sided mCRC with extrahepatic metastases (median, 15.1 months vs 11.4 months; HR, 0.66; 95% CI, 0.46-0.95 and 50.2 months vs 38.6 months; HR, 0.60; 95% CI, 0.40-0.90), but not in those with liver-limited disease (median, 14.5 months vs 15.5 months; HR, 0.79; 95% CI, 0.44-1.42 and 52.2 months vs 49.9 months; HR, 1.17; 95%, CI 0.61-2.24).

This final analysis of the DEEPER trial showed the favorable PFS and OS rates of m-FOLFOXIRI plus cetuximab in patients with RAS/BRAF wild-type and left-sided mCRC. This treatment combination may provide longer survival times as an initial therapy for patients with extrahepatic metastases.