In Australasian practice, 1 in 2 patients with LS RASwt mCRC received 1L treatment with EGFRi + doublet CT, with trends toward improved PFS and OS versus BEV + doublet CT.

We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients....In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (Pinteraction < 0.01 for PFS)….While low miR-31-3p expression could predict PFS (Pinteraction = 0.01) and OS (Pinteraction = 0.04) benefit....

A total of 76 RAS/BRAF wt mCRC patients, treated with third-line anti-EGFR-based therapy or R/T, were enrolled….A significant PFS [7.2 vs 3.6 months, HR 0.43 (95% CI 0.2-0.76), p= 0.004] and OS benefit [14.9 vs 10.9 months, HR 0.52 (95% CI 0.28-0.98), p= 0.045] in favor of anti-EGFR therapy vs R/T was observed in the L-sided tumor group....Our results demonstrated a different benefit from third-line anti-EGFR-based therapy according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T.

In terms of Progression-Free Survival (PFS), there was a benefit of anti-EGFR and anti-EGFR+CT versus CT alone (HR 0.63 [95%CrI 0.31-1.30] and 0.72 [95%CrI 0.41-1.30], respectively)....Anti-EGFR±CT maintenance therapy improves PFS and OS compared to CT alone or observation in RAS WT mCRC, with manageable safety profile.

In terms of Progression-Free Survival (PFS), there was a benefit of anti-EGFR and anti-EGFR+CT versus CT alone (HR 0.63 [95%CrI 0.31-1.30] and 0.72 [95%CrI 0.41-1.30], respectively)....Anti-EGFR±CT maintenance therapy improves PFS and OS compared to CT alone or observation in RAS WT mCRC, with manageable safety profile.

Older (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months; hazard ratio (HR) = 1.20 [0.96–1.49];p = 0.107) but inferior OS (21.3 vs 26.3; HR = 1.36 [1.08–1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3; HR = 0.82 [0.70–0.95];p = 0.008) and PFS (11.2 vs 8.9; HR = 0.70 [0.60–0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6; HR [95% confidence interval {CI}] = 0.77 [0.58–1.04];p = 0.092) and PFS (9.1 vs 8.7; HR [95% CI] = 0.85[0.63–1.15];p = 0.287). Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.

The overall survival (OS) was higher for RAS wild-type (RAS-WT) mCRC patients who received anti-EGFR, but the KRAS-WT patients compared to the anti-VEGF therapy. The results of our research indicate that superior ORR and OS between the addition of anti-EGFR therapy VS anti-VEGF therapy in all RAS-WT patients with MCRC....These results suggest that anti- EGFR monoclonal antibodies can achieve an equivalent efficacy when compared with anti-VEGF therapy of all RAS-WT mCRC patients.