TY - JOUR
T1 - Effectiveness of bevacizumab in first- and second-line treatment for metastatic colorectal cancer: ITACa randomized trial
AU - Petracci, Elisabetta
AU - Scarpi, Emanuela
AU - Passardi, Alessandro
AU - Biggeri, Annibale
AU - Milandri, Carlo
AU - Vecchia, Stefano
AU - Gelsomino, Fabio
AU - Tassinari, Davide
AU - Tamberi, Stefano
AU - Bernardini, Ilaria
AU - Accettura, Caterina
AU - Frassineti, Giovanni Luca
AU - Amadori, Dino
AU - Nanni, Oriana
N1 - Studio promosso da IRST 100%
PY - 2020
Y1 - 2020
N2 - Background: Cancer trials involving multiple treatment lines substantially increase our understanding of therapeutic strategies. However, even when the primary end-point of these studies is progression-free survival (PFS), their statistical analysis usually focuses on each line separately, or does not consider repeated events, thus missing potentially relevant information. Consequently, the evaluation of the effectiveness of treatment strategies is highly impaired.Methods: We evaluated the potentially different effect of bevacizumab (B) administered for the first- or second-line treatment of metastatic colorectal cancer (mCRC) in the ITACa (Italian Trial in Advanced Colorectal Cancer) randomized trial. The ITACa trial consisted of two arms: first-line chemotherapy (CT)+B followed by second-line CT alone versus first-line CT alone followed by second-line CT+B or CT+B+cetuximab according to KRAS status. Cox models for repeated disease progression were performed, and potential selection bias was adjusted using the inverse probability of censoring weighting method. Hazard ratios (HR) [95% confidence interval (CI)] for PFS (primary endpoint) were reported.Results: The overall effect of B across the two lines resulted in a HR = 0.80 (95% CI 0.68-0.95, p = 0.008). Evaluating the differential effect of B in first- and second-line, the addition of B to first-line chemotherapy (CT) produced a 10% risk reduction (HR = 0.90, 95% CI 0.72-1.12, p = 0.340) versus CT alone; B added to second-line CT produced a 36% risk reduction (HR = 0.64, 95% CI 0.49-0.84, p = 0.0011) versus CT alone.Conclusion: Our results seem to suggest that B confers a PFS advantage when administered in combination with second-line chemotherapy, which could help to improve current international guidelines on optimal sequential treatment strategies.
AB - Background: Cancer trials involving multiple treatment lines substantially increase our understanding of therapeutic strategies. However, even when the primary end-point of these studies is progression-free survival (PFS), their statistical analysis usually focuses on each line separately, or does not consider repeated events, thus missing potentially relevant information. Consequently, the evaluation of the effectiveness of treatment strategies is highly impaired.Methods: We evaluated the potentially different effect of bevacizumab (B) administered for the first- or second-line treatment of metastatic colorectal cancer (mCRC) in the ITACa (Italian Trial in Advanced Colorectal Cancer) randomized trial. The ITACa trial consisted of two arms: first-line chemotherapy (CT)+B followed by second-line CT alone versus first-line CT alone followed by second-line CT+B or CT+B+cetuximab according to KRAS status. Cox models for repeated disease progression were performed, and potential selection bias was adjusted using the inverse probability of censoring weighting method. Hazard ratios (HR) [95% confidence interval (CI)] for PFS (primary endpoint) were reported.Results: The overall effect of B across the two lines resulted in a HR = 0.80 (95% CI 0.68-0.95, p = 0.008). Evaluating the differential effect of B in first- and second-line, the addition of B to first-line chemotherapy (CT) produced a 10% risk reduction (HR = 0.90, 95% CI 0.72-1.12, p = 0.340) versus CT alone; B added to second-line CT produced a 36% risk reduction (HR = 0.64, 95% CI 0.49-0.84, p = 0.0011) versus CT alone.Conclusion: Our results seem to suggest that B confers a PFS advantage when administered in combination with second-line chemotherapy, which could help to improve current international guidelines on optimal sequential treatment strategies.
U2 - 10.1177/1758835920937427
DO - 10.1177/1758835920937427
M3 - Article
C2 - 32754229
VL - 12
SP - 1758835920937427
JO - Ther. Adv. Med. Oncol.
JF - Ther. Adv. Med. Oncol.
SN - 1758-8340
ER -