The predefined analysis of the primary endpoint showed FOLFIRI provided a statistically significant benefit in PFS (8.2 months) when compared with mIFL (6.0 months) or CapeIRI (5.7 months). In addition the median OS for FOLFIRI was 23.1 months, for mIFL – 17.6 months and for CapeIRI – 18.9 months. Though it did not reach statistical significance, there was a trend favoring FOLFIRI. OS benefit reflects all therapies patients may have received, including 2nd and 3rd lines. The most frequent grade 3/4 adverse events in all arms were diarrhea and neutropenia. In general the toxicity profile favored the FOLFIRI arm. Each arm had a secondary randomization to celecoxib or a placebo. In general, celecoxib neither improved efficacy nor reduced chemotherapy toxicity.
"This study provides strong evidence demonstrating the value of FOLFIRI in the management of metastatic colorectal cancer patients," said Charles Fuchs, M.D., MPH at Dana-Farber Cancer Center in Boston, MA and the lead investigator of the trial. "The data show that FOLFIRI significantly improved PFS when compared with mIFL and CapeIRI and also achieved a median OS of 23.1 months with a manageable safety profile."
The study also evaluated the impact of adding bevacizumab to FOLFIRI and mIFL. A statistically significant improvement in OS for patients treated with FOLFIRI plus bevacizumab was seen when compared with those receiving mIFL plus bevacizumab. A total of 87 percent of patients were still alive after one year compared to 61 percent of patients given mIFL plus bevacizumab. The most frequent grade 3/4 adverse events in both arms were diarrhea, neutropenia and hypertension, with neutropenia and hypertension being higher in the FOLFIRI plus bevacizumab arm.
"This study enhances our understanding of combining FOLFIRI with the targeted agent bevacizumab as a standard treatment in first-line metastatic colorectal cancer patients," said Dr. Fuchs. "FOLFIRI plus bevacizumab significantly improved OS when compared to mIFL plus bevacizumab and both regimens were tolerable."
About the BICC-C study design:
In the phase III, open-label, multi-center study, 430 patients with mCRC were randomized to receive first-line treatment with one of three CAMPTOSAR-based regimens: FOLFIRI, mIFL or CapeIRI. Of the 430 patients 144 patients received FOLFIRI (CAMPTOSAR 180 mg/m2 (D1), leucovorin 400 mg/m2 (D1), 5-FU bolus 400 mg/m2 (D1), and infusional 5-FU 2400 mg/m2 (D1) over 46 hours every two weeks), 141 patients received mIFL (modified CAMPTOSAR 125 mg/m2 (D1, 8), leucovorin 20 mg/m2 (D1, 8), and bolus 5-FU 500 mg/m2 (D1, 8) every 3 weeks), and 145 patients received CapeIRI (CAMPTOSAR 250 mg/m2 (D1) and capecitabine 1000 mg/m2 orally twice a day (D1-14) every 3 weeks). Each arm had a secondary randomization to celecoxib (400 mg orally twice a day) or a placebo in a double blind fashion. The primary endpoint was progression free survival of FOLFIRI compared to mIFL. Secondary endpoints compared the PFS, OS, response rate and safety for FOLFIRI, mIFL and CapeIRI as well as celecoxib- vs. placebo-treated patients.
In another part of the study, 117 patients with mCRC were randomized to receive first-line treatment with FOLFIRI plus bevacizumab or mIFL plus bevacizumab. 57 of these 117 patients received FOLFIRI as defined above plus bevacizumab (5 mg/kg), and 60 patients received mIFL as defined above plus bevacizumab (7.5 mg/kg). PFS, OS, response rate and safety were evaluated for both arms as part of the secondary endpoints of the study.
About CAMPTOSAR® (irinotecan hydrochloride injection)
CAMPTOSAR specifically inhibits the activity of an enzyme (topoisomerase I) essential for cancer cell division. The combination of CAMPTOSAR plus 5-FU/LV has been shown to increase survival, and has demonstrated significant improvements compared with 5-FU/LV alone in objective tumor-response rates and time-to-tumor progression. Because of the important survival benefit it provides, CAMPTOSAR remains a standard of treatment, a component for new combinations, and among the most widely studied therapies in colorectal cancer.
CAMPTOSAR is indicated as a component of 1st line therapy in combination with 5-FU/LV for the treatment of metastatic colorectal cancer. CAMPTOSAR is also indicated for patients with mCRC whose disease has recurred or progressed following initial FU-based therapy.
Both early and late forms of diarrhea can occur and may be life threatening. Late diarrhea should be managed promptly with loperamide and supportive care including antibiotics as needed. CAMPTOSAR can induce severe myelosuppression. Use of a colony-stimulating factor may be considered in patients with significant neutropenia. Particular caution should be exercised in monitoring the effects of CAMPTOSAR in the elderly (>65), in patients who have previously received pelvic/abdominal irradiation, in patients with performance status of 2 or higher and in patients known to be homozygous for the UGT1A1*28 allele. Rare cases of ileus, complicated colitis or renal impairment have been observed. It is recommended that patients receive premedication with antiemetic agents. Prophylactic or therapeutic administration of atropine should be considered in patients experiencing cholinergic symptoms. Provided intolerable toxicity does not develop, treatment with additional courses may be continued indefinitely as long as patients continue to experience clinical benefits. Thromboembolic events have been observed but the specific cause has not been determined. Full prescribing and safety information, including black box warnings, can be found at http://www.pfizer.com/pfizer/download/uspi_CAMPTOSAR.pdf.