Ramucirumab effective second-line option for NSCLC

Sep 17 2014

By Eleanor McDermid, Senior medwireNews Reporter

The monoclonal antibody ramucirumab, when added to second-line docetaxel, significantly improves the overall survival of patients with stage IV non-small-cell lung cancer (NSCLC), show the findings of the REVEL trial.

Ramucirumab binds to the vascular endothelial growth factor receptor (VEGFR)-2 extracellular domain with high affinity, preventing ligand binding and receptor activation.

“Blockade of VEGFR-2 signalling inhibits formation, proliferation, and migration of new blood vessels”, say Edward Garon (David Geffen School of Medicine at University of California, Los Angeles, USA) and study co-authors.

The team assessed the efficacy of ramucirumab in the phase III REVEL trial, comparing docetaxel combined with ramucirumab or placebo in 1253 patients with disease progression during or after first-line platinum-based chemotherapy. The patients were randomly assigned to receive docetaxel 75 mg/m² plus ramucirumab 10 mg/kg or placebo on day 1 of a 21 day cycle until disease progression, unacceptable toxicity, withdrawal or death.

Patients in the ramucirumab group had a median overall survival of 10.5 months compared with 9.1 months for those in the placebo group, giving a significant hazard ratio (HR) of 0.86. Median progression-free survival (PFS) was also significantly longer in the ramucirumab-treated patients, at 4.5 months versus 3.0 months for controls and a HR of 0.76.

Adverse events were mostly “manageable with appropriate dose reductions and supportive care”, the researchers say, with 33% of the ramucirumab group and 23% of the placebo group requiring at least one dose reduction. In the ramucirumab group, dose reductions tended to be because of neutropenia, fatigue and febrile neutropenia.

Febrile neutropenia was significantly more common in the ramucirumab than placebo groups, at 16% versus 10%. Of note, east Asian patients (Taiwan and South Korea) were particularly affected by febrile neutropenia when taking docetaxel at the 75 mg/m² dose; at a dose of 60 mg/m² their rate of febrile neutropenia was equivalent to that in non-Asian patients.

“The duration of benefit in PFS (1.5 months) and overall survival (1.4 months) was much the same, suggesting that the delay in progression did not just extend time on drug but translated to a clinically meaningful additional duration of survival in this group of previously treated patients”, the researchers write in The Lancet Oncology.

In an accompanying comment, however, Tony Mok (State Key Laboratory in Oncology, South China), and Herbert Loong (The Chinese University of Hong Kong), note that approximately a sixth of patients in both treatment groups were subsequently given epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).

Noting that EGFR mutation status data was incomplete for the patients, they caution: “A small imbalance in the number of patients harbouring EGFR mutations and exposed to EGFR TKIs in subsequent lines of treatment could have led to a significant bias in overall survival.”

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