• Oncology Clinical Trials
• Gastrointestinal Cancers

• Oncology Clinical Trials
• Gastrointestinal Cancers
• Oncology

Cross-talk between vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) are involved in tumor growth and survival; inhibition of either may increase survival in patients with metastatic colorectal cancer (mCRC). However, combining monoclonal antibodies (mAb) targeting VEGF or EGFR in mCRC has not been effective [Hecht JR et al. J Clin Oncol. 2009; Tol J et al. N Engl J Med. 2009]. Benoit Chibaudel, MD, Saint-Antoine Hospital, Paris, France, reported the final results of the Optimized Chemotherapy Followed by Maintenance With Bevacizumab With or Without Erlotinib in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery study [DREAM; NCT00265824].

DREAM was a randomized, phase 3 trial in patients with unresectable mCRC testing the combination of bevacizumab (BEV), a mAb that targets VEGF, with erlotinib (ERL), a tyrosine kinase inhibitor targeting EGFR, as maintenance therapy in mCRC.

All patients (n = 694) received 1 of 3 induction regimens, all of which contained BEV, and only those patients whose disease did not progress (n = 452 or 65% of the registered population) were randomly assigned to maintenance therapy with BEV (n = 228) or BEV + ERL (n = 224). The primary end point was progression-free survival (PFS) from randomization. Secondary end points included overall survival (OS), PFS from registration, response according to KRAS status, and adverse events.

Baseline characteristics were similar between treatment arms at registration and at randomization. The induction response rate was 55% complete or partial response for patients randomized to BEV vs 58% for those randomized to BEV + ERL; stable disease was 46% vs 42%, respectively. The treatment delivery was similar for both arms, but the BEV + ERL arm received 12% more BEV cycles and 30% of the ERL doses given were a reduced dose. Results at a median follow-up of 50 months of maintenance therapy are shown in Table 1. BEV + ERL was generally favored for maintenance PFS and OS in a subgroup analysis. Maintenance response rates were significantly higher with BEV + ERL, including among the subgroup of patients with mutant KRAS.

There was increased toxicity of any grade in the BEV + ERL arm for nausea, mucositis, diarrhea, and skin rash. Grade 3/4 toxicities were increased for diarrhea, skin rash, and nausea in the BEV + ERL arm.

The same proportion of patients in both arms received the same postprogression therapy, including oxaliplatin reintroduction, irinotecan-based second-line therapy, or anti-EGFR mAb. Survival in patients who received postprogression therapy, including anti-EGFR mAb, is similar in both arms.

In patients with mCRC, induction therapy followed by maintenance therapy with BEV + ERL significantly improves maintenance PFS, PFS from registration, OS from maintenance, and OS from registration compared with the same induction therapy followed by BEV monotherapy. This effect is independent of the KRAS mutational status; a significant difference in response rate is observed during the chemotherapy-free maintenance therapy in KRAS mutated tumors.

The safety of BEV + ERL is acceptable despite increased incidence of severe skin rash and diarrhea. The survival benefit for BEV + ERL is independent of the subsequent therapy. Anti-EGFR mAb remains active in patients who received prior erlotinib. BEV and a short period of ERL therapy may provide a new treatment option in first-line therapy following induction chemotherapy with BEV for patients with unresectable mCRC.

• © 2014 MD Conference Express®