Ramucirumab Results RAISE Metastatic CRC Overall Survival

Ramucirumab plus FOLFIRI boost overall survival for metastatic CRC patients who have failed bevacizumab and chemotherapy

medwireNews: RAISE trial results support the second-line use of ramucirumab and FOLFIRI chemotherapy in patients with metastatic colorectal cancer (CRC) who experience disease progression within 6 months of completing first-line bevacizumab with oxaliplatin and fluoropyrimidine.

The research demonstrates significantly improved overall survival (OS) for the patients who were randomly assigned to continue with a treatment targeting the vascular endothelial growth factor (VEGF)-A–VEGF receptor (VEGFR) pathway compared with those given FOLFIRI with placebo.

Median OS was 13.3 months for the ramucirumab-treated patients versus 11.7 months for the placebo group, giving a significant hazard ratio of 0.84, report Josep Tabernero, from Universitat Autònoma de Barcelona in Spain, and co-workers.

Of note, the survival benefit associated with ramucirumab was found to be consistent across patient subgroups including age and ethnicity, KRAS exon 2 status, time to disease progression from the start of first-line therapy, site of primary tumour and number of metastatic sites.

Progression-free survival was also significantly better for the ramucirumab group compared with controls, at 5.7 versus 4.5 months and a hazard ratio of 0.79, the team says in The Lancet Oncology.

Patients given ramucirumab had a significantly higher rate of grade 3 or worse adverse events than those given placebo, at 79% versus 62%, with higher rates of neutropenia and hypertension but comparable rates of diarrhoea, fatigue and febrile neutropenia.

“The RAISE trial design was appropriate for a second-line population and can be generalised to clinical practice”, write Josep Tabernero and co-authors.

“Our results confirmed the benefit of continuing inhibition of angiogenesis from first-line to second-line therapy with ramucirumab and validated the strategy of blocking the VEGF receptor to improve survival of patients with metastatic colorectal cancer.”

However, Timothy Price, from Queen Elizabeth Hospital in Woodville in South Australia, notes in an accompanying comment that the increased use of anti-epidermal growth factor receptor inhibitors and irinotecan as first-line treatments for advanced CRC means the RAISE population may be less representative of clinical practice.

Further research is needed to determine whether continuing VEGF blockade is the best option for patients with KRAS wild-type tumours or whether ramucirumab may be an alternative to bevacizumab for patients with BRAF mutations, he writes.


Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 2015; Advance online publication 12 April. doi: dx.doi.org/10.1016/S1470-2045(15)70127-0

Price TJ. Second-line therapy for metastatic colorectal cancer. Lancet Oncol 2015; Advance online publication 12 April. doi: dx.doi.org/10.1016/S1470-2045(15)70169-5

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