September 2013, Vol 2, No 6

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Bevacizumab Maintenance Improves Survival in mCRC, but Added Erlotinib Is of No Value

Alice Goodman

Uncategorized

Bevacizumab maintenance therapy following induction with bevacizumab-based chemotherapy significantly increases progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). However, the addition of erlotinib in the maintenance phase does not increase overall survival (OS) compared with bevacizumab alone. KRAS status was not a predictor of benefit from erlotinib in this study. A continuous strategy of induction chemotherapy followed by maintenance with bevacizumab-based therapy achieves a median OS of 25 months.

These results from the phase 3 GERCOR DREAM trial were presented at the 2013 Annual Meeting of ASCO by Christophe Tournigand, MD, PhD, Hôpital Saint-Antoine, Paris, France.

The rationale for combining bevacizumab and erlotinib in the GERCOR DREAM trial was based on the following observations: combining a TKI-inhibiting VEGFR agent with an anti-EGFR agent has synergistic activity, even in a KRAS-mutated model. Bevacizumab, a VEGF inhibitor, increases survival in mCRC when combined with oxaliplatin- or irinotecan-based first- or second-line chemotherapy. Cross-talk between the EGFR and VEGF pathways is involved in tumor growth and survival.

The study enrolled 700 patients with mCRC treated with 1 of 3 oxaliplatin- or irinotecan-based regimens: mFOLFOX7 (leucovorin, oxaliplatin, 5-fluorouracil), XELOX2 (capecitabine, oxaliplatin), or FOLFIRI (leucovorin, 5-fluorouracil, irinotecan); bevacizumab was combined with all 3 regimens. Patients who had no progression of disease following chemotherapy were randomized to maintenance therapy with bevacizumab 7.5 mg/kg every 3 weeks + erlotinib 150 mg/day (n=224) or beva­cizumab alone at the same dose and regimen (n=228); treatment was continued until disease progression.

Baseline characteristics were similar between the treatment arms; ~27% were aged 70 years or older; ~57% were male; ~9% had previous adjuvant chemotherapy; ~18% were metachronous; and ~60% were performance status 0.

No significant difference in PFS between maintenance treatment arms was observed. Maintenance PFS from randomization was a median of 4.6 months with bevacizumab alone versus 5.9 months with bevacizumab + erlotinib. PFS (from registration in the trial) was 9.3 months versus 10.2 months, respectively. Also, OS was not improved by the addition of erlotinib. OS from registration was 27.9 months versus 28.4 months, respectively.

For the KRAS analysis, wild-type KRAS was found in 111 patients in the bevacizumab maintenance therapy group and in 129 patients in the bevacizumab + erlotinib maintenance group. As in the main analysis of the trial, no significant differences in maintenance treatment arms were observed for PFS and OS in patients with wild-type KRAS and those with mutated KRAS, demonstrating that KRAS does not select for patients who will benefit from erlotinib.

Reference
Tournigand C, Chibaudel B, Samson B, et al. Maintenance therapy with bevacizu­mab with or without erlotinib in metastatic colorectal cancer (mCRC) according to KRAS: results of the GERCOR DREAM phase III trial. J Clin Oncol. 2013;31(suppl):Abstract 3515.

Uncategorized - September 23, 2013

Genomic Sequencing Uncovers the Genetic Landscape of Primary CNS Lymphoma: Will likely lead to new targeted therapies for an incurable malignancy

Lugano, Switzerland – The genomic basis of primary central nervous system lymphoma (PCNSL), a very aggressive and incurable type of lymphoma, has not been understood until now. At the 2013 International Conference on Malignant Lymphoma, a team of researchers from the Mayo Clinic and from the University of Virginia presented [ Read More ]

Immunotherapy - September 23, 2013

How Do Melanoma Experts Use the New Agents?

Melanoma experts gathered at the second annual World Cutaneous Malignancies Congress to debate the optimal means of treating melanoma using the new agents and to share predictions about the future treatment landscape in metastatic melanoma. Their insights are shared in this report. Metastatic Melanoma: Which Drug First? Despite excitement over [ Read More ]