FOLFOXIRI plus bevacizumab improves response rate, PFS in advanced colorectal cancer

COPENHAGEN, Denmark —The addition of irinotecan to FOLFOX chemotherapy and bevacizumab improved response rates and prolonged PFS for the first-line treatment of advanced colorectal cancer, according to results of the randomized phase 2 CHARTA trial presented at the European Society for Medical Oncology Congress.

These findings replicate results from the TRIBE trial and further support the use of the four-drug FOLFOXIRI regimen for the first-line treatment of these patients, according to the researchers.

Hans-Joachim Schmoll , MD, PhD of the department of internal medicine IV, hematology and oncology at University Clinic Halle (Saale), Martin Luther University Halle-Wittenberg, and colleagues evaluated data from 250 patients (median age, 61 years; 65% men) with an ECOG performance status of 0 (96%) to 2 (4% score of 1 or 2) and at least one measureable lesion larger than 1 cm. Patients were stratified based on whether they were classified as having ESMO Group 1 (29%), 2 (55%) or 3 (16%) disease.

Researchers randomly assigned patients to receive standard FOLFOX chemotherapy (folinic acid, fluorouracil and oxaliplatin) and bevacizumab (Avastin, Genentech) alone, or with the addition of irinotecan to FOLFOX, also known as FOLFOXIRI chemotherapy. In the FOLFOX group, 51.5% had left-sided tumors and 45% had right-sided tumors; in the FOLFOXIRI group, 48.5% had left-sided tumors and 55% had right-sided tumors.

Patients received induction treatment for 6 months and maintenance for 12 months, or until disease progression.

PFS at 9 months served as the study’s primary endpoint, where P < .1 indicated the endpoint had been met. Response rate, median PFS and OS served as secondary endpoints.

Evaluable data were available from 241 patients.

Overall, the rate of 9-month PFS was 68% in the FOLFOXIRI arm and 56% in the FOLFOX arm (P = .086), indicating that the primary endpoint had been met.

Further, median PFS was 12 months in the FOLFOXIRI arm and 9.76 months in the FOLFOX arm and, which was comparable to results from the TRIBE trial (12.1 months vs. 9.7 months).

More patients in the FOLFOXIRI arm achieved complete or partial response (70% vs. 60%) and fewer experienced progressive disease (9% vs. 14%). Rate of complete response was the same in both arms (5% for both), and rates of stable disease were lower with FOLFOXIRI (21% vs. 25%).

Preliminary OS data showed median survival was 27.9 months with FOLFOXIRI and 24.9 months with FOLFOX.

Subgroup analyses showed no differences in outcomes, except that patients with right-sided tumors achieved longer PFS than patients with left-sided tumors (12 months vs. 10.4 months; HR = 0.69; P = .03).

Further, researchers observed nonsignificant improvements in PFS among patients with ESMO group 3 disease (HR = 0.51), RAS wild-type disease (HR = 0.67) and an ECOG score of 1 (HR = 0.69).

Seventeen percent of patients required an initial dose reduction. More patients assigned FOLFOXIRI received 90% or greater dose intensity (36% vs. 18%).

Most toxicity was low to moderate in nature. More patients assigned FOLFOXIRI experienced grade 3 or grade 4 diarrhea (16% vs. 12%), neutrophils (20% vs. 14) and gastrointestinal toxicity (20% vs. 12%). – by Alexandra Todak

Reference:

Schmoll H, et al. Abstract LBA22. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.

Disclosure: Roche funded this study. The researchers report no relevant financial disclosures.