First-line treatment of advanced colorectal cancer with FOLFOXIRI chemotherapy plus Avastin (bevacizumab) in a Phase 2 clinical trial showed improvements in patient response rate and progression-free survival, according to recently presented results.
The data, shown at the European Society for Medical Oncology (ESMO) 2016 Congress Oct. 7-11 in Denmark, revealed that the addition of Camptosar (irinotecan) to FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy is a better approach than using FOLFOX alone.
The results are in line with results of the Phase 3 TRIBE trial (NCT00719797) that evaluated FOLFOXIRI plus Avastin versus FOLFIRI chemotherapy plus Avastin, which showed a 20% reduction in the risk of death in the FOLFOXIRI group.
In the randomized, open-label Phase 2 CHARTA trial (NCT01321957), Dr. Hans-Joachim Schmoll, MD, PhD, of Germany’s University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, and his colleagues addressed the effectiveness of Camptosar in addition to the FOLFOX chemotherapy combined with Avastin, a monoclonal antibody that targets vascular endothelial growth factor and prevents the formation of new tumor vessels.
The trial enrolled 250 patients (65% male, median age 61) who had at least one measurable lesion larger than 1 cm. In the ECOG performance test, which measures cancer patients’ level of function such as their ability to care for themselves and to participate in daily activities including walking and working, 96% tested as fully capable.
Participants were randomized to receive either FOLFOX chemotherapy and Avastin or with the addition of Camptosar to FOLFOX, known as FOLFOXIRI chemotherapy.
At baseline, the FOLFOX group was composed of 51.5% of patients with left-sided tumors and 45% with right-sided tumors. In the FOLFOXIRI group, 48.5% had left-sided tumors and 55% had right-sided tumors.
Patients received induction treatment for six months and maintenance for 12 months, or until their disease progressed. The study’s primary endpoint was progression-free survival (PFS) at nine months. Secondary endpoints included median PFS, response rate, and overall survival.
Data from the 241 evaluable patients revealed a significant improvement in the study’s primary endpoint. The FOLFOXIRI group showed a nine-month PFS of 68% compared to 56% in the FOLFOX group.
Median PFS, response rates, and overall survival were also higher in the FOLFOXIRI group. Patients in the FOLFOXIRI arm had a median PFS of 12 months when compared to 9.76 months PFS in the FOLFOX arm — which was similar to the results from the TRIBE trial (12 months vs. 9.7 months).
Overall response rates were higher in the FOLFOXIRI group (70% vs. 60%), but complete response rates were similar in both groups (5% for both). Fewer patients reached stable disease in the FOLFOXIRI group than in the FOLFOX group (21% vs. 25%), but fewer patients experienced progressive disease (9% vs. 14%).
Preliminary results showed improvements in overall survival — 27.9 months in the FOLFOXIRI arm and 24.9 months of the FOLFOX arm.
The researchers also noted that patients with right-sided tumors had longer PFS rates than those with left-sided tumors (12 months vs. 10.4 months), suggesting that patient outcomes would be even better in the FOLFOXIRI group if adjusted by the location of the tumor.
Treatment-induced adverse effects were low to moderate, but more patients in the FOLFOXIRI group experienced decreases in white blood cells, diarrhea, and gastrointestinal toxicity.
