Induction treatment in first-line with chemotherapy + bevacizumab (bev) in metastatic colorectal cancer: Results from the gercor-DREAM phase III study.

Abstract

457 Background: the DREAM study compares a maintenance therapy with bevacizumab (bev) alone or with the erlotinib after a bev-based induction therapy with FOLFOX, or biweekly XELOX or FOLFIRI. Efficacy of the induction treatment is reported here. Methods: Patients (pts) with previously untreated metastatic colorectal cancer received one of the following regimen (investigator’s choice): mFOLFOX7-bev, biweekly mXELOX-bev or FOLFIRI-bev. Oxaliplatin was administered no more than 6 cycles. In the 1st cohort, pts received 3 months (m) of FOLFOX-bev or mXELOX-bev before randomization. In the 2nd cohort, pts received 3m of FOLFOX-bev or mXELOX-bev then 3 m of fluoropyrimidine-bev, or 6 m of FOLFIRI-bev before randomization. Pts with disease control were then randomized between bev alone or with erlotinib until progression. Results: FOLFOX-bev was administered in 424 pts, mXELOX-bev in 203 pts and FOLFIRI-bev in 67 pts. Pts characteristics for the whole population are: median age 63 yrs (26-80), male/female 59.8%/40.2%, synchronous mets/metachronous 82.6%/17.4%, PS 0/1/2 58%/39%/3%, LDH>UNL 53%, platelets >400000/mm3 27%. Patients received a median nb of 6 cycles of oxaliplatin for FOLFOX-bev and mXELOX-bev, and a median nb of 12 cycles of irinotecan with FOLFIRI-bev. Response rates are respectively 48%, 50% and 63%. Median PFS are respectively 8.61m, 8.97m and 9m. Severe toxicity profiles (grade 3-4) appear to be different according to the schedule : more neutropenia and diarrhea with FOLFIRI-bev, HFS and diarrhea with mXELOX-bev and neuropathy with FOLFOX-bev. Conclusions: Modified biweekly XELOX-bev provides similar efficacy results with FOLFOX-bev, and FOLFIRI-bev as induction therapy in first-line. Clinical trial information: NCT00265824.

Long Term Maintenance Therapy with VEGF Inhibitor with Remission of the Disease for Seven Years in Patient with Metastatic Rectal Cancer

“…The DREAM study was multicentre Phase 3 study that compared maintenance therapy with Bevacizumab (7.5 mg/kg every 3 weeks) + erlotinib (150 mg/day) (n=224) with single agent Bevacizumab (n=228) after induction therapy with investigators choice of Bevacizumab (5 mg/kg every 2 weeks) + mFOLFOX7 modified FOLFOX (n=429), biweekly mXELOX modified XELOX (n=204), or FOLFIRI 5fluorouracil/leucovorin/ irinotecan (n=67) in 700 previously untreated patients with mCRC. The primary end point of maintenance PFS was significantly improved Bevacizumab + erlotinib compared with single agent Bevacizumab maintenance therapy (5.9 moths vs 4.9 months, HR 0.77, p=0.012) [12].…”

“…Bevacizumab is associated with a broad spectrum of adverse effects and may be fatal in a small number of cases. Across Phase 3 studies, adverse events reported as very common and common with Bevacizumab included gastrointestinal perforation, thromboembolic events, hypertension, neutropenia, febrile neutropenia, proteinuria, Bleeding, leukopenia, diarrhea, vomiting, nausea, anemia, thrombocytopenia, cardiac disorders, neurotoxicity, hand-foot syndrome, fatigue, abdominal pain, fever, neuropathy, rash, ileus, dehydration, headache, dyspnea, mucositis [6][7][8][9][10][11][12][13]. Some of these adverse effects are described when bevacizumab is used as combination wich chemotherapeutic agents, like the tromboembolic events, as was the case with our patients.…”