Primary tumor sidedness and negative hyperselection to modulate anti-EGFR-based maintenance strategies in patients with RAS wild-type metastatic colorectal cancer: individual patient data pooled analysis of two randomized clinical trials.

BACKGROUND

Patients with RAS wild-type (WT), left-sided metastatic colorectal cancer (mCRC), negatively hyperselected for anti-EGFR resistance alterations, benefit most from anti-EGFR-based first-line treatment. The predictive impact of these stratification parameters on maintenance strategy efficacy is unclear.

METHODS

This pooled analysis included individual patient data from the PanaMa (NCT01991873) and Valentino (NCT02476045) phase 2 trials. Patients with RAS WT mCRC received FOLFOX plus Panitumumab induction therapy followed by maintenance with 5-fluorouracil/leucovorin (5-FU/LV) plus Panitumumab vs. 5-FU/LV monotherapy (PanaMa) or Panitumumab monotherapy (Valentino). Outcomes included progression-free survival (PFS) and overall survival (OS). Subgroup analyses examined primary tumor sidedness (left vs. right) and hyperselection status (negative vs. altered).

RESULTS

Among 607 patients receiving induction, sidedness and hyperselection status were available for 589 and 511 patients, respectively. Left-sided and negative hyperselected tumors were observed in 80.2% and 63.9% of patients, respectively. Panitumumab-based maintenance improved PFS in left-sided, negative hyperselected patients compared to 5-FU/LV alone, with no OS differences. PFS and OS were comparable for Panitumumab alone vs. Panitumumab plus 5-FU/LV.

CONCLUSION

Tumor sidedness and hyperselection status significantly influence maintenance strategy efficacy in mCRC. For left-sided, negative hyperselected patients, Panitumumab monotherapy may optimize efficacy while minimizing toxicity. Further investigation into the relative contribution of individual hyperselection parameters in this setting is warranted.