Impact of chemotherapy partner on efficacy of targeted agents in metastatic colorectal cancer (mCRC): Systematic review and meta-analysis (#92)
Background: The question of whether efficacy of targeted therapy is affected by chemotherapy (chemo) partner in mCRC remains unresolved. Studies of chemo added to EGFR inhibitors (EGFRI: cetuximab, panitumumab) and anti-VEGF agents (bevacizumab, aflibercept) have reported varied outcomes. We undertook systematic review to explore efficacy of these combinations according to chemo partner.
Methods: Randomized controlled trials in mCRC were sought evaluating the combination of chemo with targeted therapy, categorized according to therapy class (EGFR or VEGF) and chemo partner (oxaliplatin (ox) or irinotecan (iri)). The impact of fluoropyrimidine (FP) regimen (bolus, infusional or oral) was also explored. Only KRAS exon 2 WT subpopulations were included in EGFR analysis. The primary endpoint was overall survival (OS) with secondary endpoints of progression-free survival (PFS), overall response rate (ORR) and toxicity. Meta-analysis was performed according to standard methods with hazard ratios (HR) and odds ratios (OR) computed.
Results: We identified 21 trials evaluating 9857 patients. For EGFRI, OS (8 trials, 3492 pts) was improved in combination with iri (HR 0.90, 95% CI 0.81-1.00, p=0.04) but not ox (HR 0.97, 95% CI 0.87-1.09, p=0.62). PFS (n=3473) was also improved with iri (HR 0.77, 95% CI 0.69-0.86, p<0.00001) but not ox (HR 0.92, 95% CI 0.83-1.02, p=0.13). The iri-ox interaction p-value was 0.32 for OS and 0.06 for PFS. This interaction was no longer significant when analysis was restricted to infusional-only regimens.
For anti-VEGF therapy (11 studies, 6103 pts), significant OS and PFS benefit was found for both iri and ox backbones. Iri-ox interaction was present for PFS (I2=83%, p=0.003) favouring iri. Two trials (n=151) directly compared iri-EGFRI with ox-EGFRI. No significant differences in efficacy were observed.
Conclusions: The meta-analysis shows superior efficacy when EGFRI are combined with irinotecan-based chemotherapy regimens compared to oxaliplatin-based regimens. This may be due to factors such as choice of FP.