Bevacizumab Plus Erlotinib Studied As Maintenance Option For Metastatic CRC

Bevacizumab plus erlotinib may offer maintenance survival benefits for patients with unresectable, metastatic colorectal cancer

medwireNews: Combining the anti-angiogenesis inhibitor bevacizumab with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib may lengthen survival in patients with metastatic colorectal cancer (CRC) who have responded to induction therapy, suggest phase III trial findings published in The Lancet Oncology.

At the primary analysis, progression-free survival (PFS) was a comparable 5.1 months for the 224 patients randomly assigned to receive bevacizumab plus erlotinib who achieved at least stable disease using bevacizumab induction treatment and 6.0 months for the 228 patients given bevacizumab alone.

However, the trial investigators report that the PFS curves began to separate after 5 months and by the final analysis, after a median of 48.3 months of follow-up in the combined treatment group and 51.0 months for those given bevacizumab alone, median PFS was significantly higher for patients given bevacizumab plus erlotinib, at 5.4 months versus 4.9 months and a stratified hazard ratio (HR) of 0.81.

Overall survival (OS) from maintenance was also significantly higher with bevacizumab plus erlotinib than bevacizumab alone at the final analysis, at a median of 24.9 months and 22.1 months, respectively, and a stratified HR of 0.79.

Patients given the combined maintenance regimen had significantly more grade 3 or more severe events than those given bevacizumab alone, including skin rash (21 vs 0%), diarrhoea (10 vs <1%) and asthenia (5 vs <1%). Treatment was discontinued because of adverse events by 8% and 3% of the combined and single therapy groups, respectively.

“Despite some toxicity, bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with metastatic colorectal cancer following bevacizumab-based induction therapy”, write Aimery de Gramont, from Institut Hospitalier Franco-Britannique in Levallois-Perret, France, and co-investigators.

“Further research should focus on predictive biomarkers for EGFR inhibition and erlotinib and explore sequential administration of the different maintenance regimens either after induction therapy or after induction therapy and second-line therapy.”

In an accompanying comment,Fortunato Ciardiello, from Seconda Università degli studi di Napoli in Italy,observes that previous trials of combined EGFR and vascular endothelial growth factor inhibitors have failed to show efficacy.

“[T] his study is the first to assess the combined inhibition of EGFR and angiogenesis in a maintenance phase of treatment, after a major tumour response has occurred; this therapeutic approach could be more effective in controlling tumour growth at this stage compared with first-line treatment”, he writes.

“Furthermore, a small molecule tyrosine kinase inhibitor might be more active in combination with bevacizumab than a blocking monoclonal antibody”, says the commentator, noting that this is in line with phase II results for lung cancer patients given bevacizumab plus erlotinib compared with erlotinib alone.

Nevertheless, Fortunato Ciardiello concludes that “more clinical studies are needed to define the effectiveness of this approach in the continuum of care for patients with metastatic colorectal cancer.”

Reference

Tournigand C, Chibaudel B, Samson B, et al. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3) : a randomised, open-label, phase 3 trial. Lancet Oncol 2015; Advance online publication 13 October. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00216-8

Ciardiello F. Maintenance therapy for metastatic colorectal cancer. Lancet Oncol 2015; Advance online publication 13 October. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00308-3

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