DOI: 10.1200/oa-24-00080 ISSN: 2994-9750

Response to Biologics in Patients With Early-Onset Treatment-Naïve Metastatic Colorectal Cancer—An Aide et Recherche en Cancérologie Digestive Database Analysis

Zhaohui Jin, Jesse G. Dixon, Joleen M. Hubbard, Cathy Eng, Christopher H. Lieu, Jean-Yves Douillard, Richard A. Adams, Timothy S. Maughan, Eric Van Cutsem, Alan P. Venook, Heinz-Josef Lenz, Volker Heinemann, Sabstian Stintzing, Leonard B. Saltz, Hans-Jacchim Schmoll, Charles S. Fuchs, Randolph Hecht, Alfredo Falcone, Eduard Diaz-Rubio, Cornelis J.A. Punt, Niall C. Tebbutt, Carsten Bokemeyer, Benoist Chibaudel, John Zalcberg, Takayuki Yoshino, Aimery De Gramont, Qian Shi
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PURPOSE

Colorectal cancer (CRC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (<50 years, named early-onset CRC [eoCRC]) has been increasing.

PATIENTS AND METHODS

Individual patient data on 13,365 patients with metastatic CRC enrolled between 2000 and 2012 in 17 first-line randomized trials in the Aide et Recherche en Cancérologie Digestive database were pooled. The distribution of demographics, clinicopathologic features, biomarkers, and outcome data were summarized and compared by age groups. Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for potential confounders. Predictive value of age group on clinical outcomes was evaluated by testing interaction effect between treatment and age variables.

RESULTS

Overall, 2,045 patients with eoCRC (median age, 42.5) and 11,320 patients with average-onset CRC (aoCRC; median age, 63.8) were included in this analysis. Within the eoCRC population, treatment with bevacizumab in addition to chemotherapy improved PFS (9.9 v 6.8 months; hazard ratio [HR], 0.66 [95% CI, 0.54 to 0.80]; P < .0001), which was similar to the findings in aoCRC population (9.4 v 7.3 months; HR, 0.73 [95% CI, 0.67 to 0.80]; P < .001; interaction P = .5415). However, epithelial growth factor receptor inhibitor (EGFRi) did not improve PFS in RAS wild-type (WT) patients with eoCRC who had left-sided primary tumors (8.3 v 8.9 months; HR, 1.20 [95% CI, 0.81 to 1.77]; P = .36), whereas EGFRi significantly improved PFS in the aoCRC population (9.9 v 8.5 months; HR, 0.74 [95% CI, 0.64 to 0.86]; P < .0001; interaction P = .083).

CONCLUSION

Treatment-naïve patients with metastatic eoCRC appear to derive similar benefit from bevacizumab as patients with aoCRC. However, patients with eoCRC with left-sided RAS/RAF WT tumors did not appear to derive benefit from first-line EGFRi.

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