TRIPLETE trial

Background

Phase 3 RCT. 435 patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer (mCRC). Tested whether intensifying the chemotherapy backbone (FOLFOXIRI vs FOLFOX) added to panitumumab improves objective response.

Interventions and follow up

Arm A: mFOLFOXIRI + panitumumab 6 mg/kg Q2W ×12 cycles, then 5-FU/panitumumab until progression
Arm B: mFOLFOX + panitumumab ×12 cycles, then 5-FU/panitumumab until progression
Primary endpoint: Objective response rate (ORR)
Median follow-up: 26.5 mo

Results

ORR: 73% (arm A) vs 76% (arm B); OR 0.87, 95% CI 0.56–1.34, P=.526
mPFS: 12.7 mo (arm A) vs 12.3 mo (arm B)

Adverse events

Overall/GI: Grade 3–4 events 69% (arm A) vs 57% (arm B); diarrhea 23% vs 7%; stomatitis 7% vs 7%
Skin: Grade 3–4 rash 19% (arm A) vs 29% (arm B)

Conclusions

Intensifying the chemotherapy backbone to FOLFOXIRI added to panitumumab did not improve ORR over FOLFOX + panitumumab in RAS/BRAF wild-type mCRC, while increasing gastrointestinal toxicity. FOLFOX + panitumumab remains the preferred doublet partner.

Key Limitations

Both arms used panitumumab, so the trial addresses chemotherapy intensity rather than the value of anti-EGFR therapy itself. The high baseline ORR with FOLFOX/panitumumab left little room to demonstrate incremental benefit. Sidedness was not the primary stratifier despite its prognostic/predictive importance in anti-EGFR therapy.

Clinical Context

TRIPLETE established that a doublet (FOLFOX) plus panitumumab, not a triplet, is the optimal first-line chemotherapy partner for anti-EGFR therapy in RAS/BRAF wild-type mCRC. ESMO recommends doublet + anti-EGFR for fit patients with left-sided RAS/BRAF wild-type disease; triplet intensification is reserved for use with bevacizumab (TRIBE/TRIBE2) rather than EGFR antibodies.

References