KEY TAKEAWAYS
- The DEEPER phase 2 trial aimed to assess the efficacy of m-FOLFOXIRI + cet in pts with mutant mCRC.
- The primary endpoint was to determine DpR.
- The m-FOLFOXIRI + cet had shorter PFS than m-FOLFOXIRI + bev; DpR was similar.
The randomized trial has demonstrated a significantly better depth of response (DpR) in m-FOLFOXIRI + cetuximab (cet) vs bevacizumab (bev) as an initial therapy in RAS wild-type (wt) patients (pts) with metastatic colorectal cancer (mCRC). In left-sided and RAS/BRAF wt pts, progression-free survival (PFS) was better in the cet arm (median; 14.5 vs. 11.9 months, HR 0.71). This trial reported the efficacy of m-FOLFOXIRI + cet in mCRC pts with right-sided or BRAF mutant tumors.
Yu Sunakawa and the team investigated efficacy of m-FOLFOXIRI + cet in pts with right-sided or BRAF mutant mCRC.
Researchers enrolled primary endpoint evaluable pts, DpR in per-protocol set (PPS). The secondary endpoints comprised PFS, overall survival (OS), overall response rate (ORR), early tumor shrinkage rate, resection rate, and toxicity assessments.
The stratification criteria was the tumor sidedness and a factor for patient randomization, while BRAF status was determined in 73% of PPS pts through medical record review or biomarker analysis. All statistical analyses employed 2-sided tests, with significance defined as P ≤ 0.05.
The results demonstrated that in the PPS of 321 pts, 52 were right-sided and 22 had BRAF mutant tumors. Among right-sided pts, the median DpR was 50.0% in the cet arm versus 41.2% in the bev arm (P=0.47). In BRAF mutant pts, the median DpR was 45.7% with cet versus 38.3% with bev (P=0.77). Sub-group analysis by sidedness and BRAF status revealed varying DpR: 53.3% versus 58.9% for right-sided wt 46.7% vs 28.2% for right-sided mutant, and 20.3% versus 56.9% for left-sided mutant.
The ORR and R0 resection rates did not significantly differ between the two treatment arms in right-sided or BRAF mutant pts. Median PFS among right-sided pts was 9.0 months with cet versus 12.8 months with bev (HR 1.54, P=0.14). In BRAF wt right-sided pts, PFS favored the bev arm (median 14.7 vs. 9.7 months). Among BRAF mutant pts, PFS was significantly shorter with cet compared to bev (median 4.6 vs. 8.4 months, HR 4.65, P=0.0016). Furthermore, worse PFS outcomes were observed in the cet arm for both left and right primary tumor sites.
The study concluded that in metastatic colorectal cancer pts with right-sided tumors or BRAF mutations, m-FOLFOXIRI + cet led to inferior PFS compared to m-FOLFOXIRI + bev, despite comparable depth of response. Furthermore, the addition of cetuximab to the triplet regimen did not provide clinical benefit in left-sided metastatic colorectal cancer pts harboring BRAF mutant tumors.
The trial was sponosred by Japan Clinical Cancer Research Organization.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://www.clinicaltrials.gov/study/NCT02515734
Sunakawa Y, Shiozawa M, Kawai T, et al. (2024). “Modified (m)-FOLFOXIRI plus cetuximab versus bevacizumab for right-sided or BRAF mutant metastatic colorectal cancer (mCRC): Subgroup analysis of the DEEPER trial (JACCRO CC-13).” Presented at ESMO-GI 2024, (Abstract 38P)
