Ramucirumab Combination Improves OS and PFS in NSCLC

The second-line administration of ramucirumab in combination with docetaxel has shown a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared with placebo plus docetaxel in patients with non-small cell lung cancer (NSCLC), Eli Lilly and Company, the developer of the agent, announced today.

The phase III REVEL randomized double-blind trial compared ramucirumab and docetaxel to placebo and docetaxel in patients with NSCLC whose disease had progressed after failure of prior platinum-based chemotherapy for locally advanced or metastatic disease. More than 1200 patients were enrolled across 26 countries with both squamous and nonsquamous NSCLC.

"We are pleased with these phase III data of ramucirumab in non-small cell lung cancer, which accounts for most cases of lung cancer — the leading cause of cancer-related mortality worldwide. Despite currently available therapies, there continues to be a need for new second-line treatment options for patients with lung cancer," Richard Gaynor, MD, senior vice president, product development and medical affairs for Lilly Oncology said in a press release. "REVEL is the first positive Phase III study of a biologic in combination with chemotherapy to demonstrate improved overall survival compared to chemotherapy alone in second-line non-small cell lung cancer."

The most common (>5% incidence) grade >3 adverse events occurring at a higher rate on the ramucirumab plus docetaxel arm compared to the control arm were decreased white blood cell count (neutropenia/leukopenia), febrile neutropenia, fatigue/asthenia, and hypertension.

Full data from the REVEL trial will be announced at an upcoming scientific meeting and Lilly said it intends to submit the first application of these data to regulatory authorities this year.

Ramucirumab is a fully human monoclonal antibody that targets vascular endothelial growth factor (VEGF) receptor-2. It is designed to directly inhibit angiogenesis, a process by which blood vessels supply blood to tumors.

In an open-label phase II study of 140 chemotherapy-naive patients, ramucirumab was investigated in combination with first-line chemotherapy in advanced nonsquamous NSCLC.

For patients who received pemetrexed (500 mg/m²) plus carboplatin (AUC=6) or cisplatin (75 mg/m²) once every three weeks, the median PFS was 4.3 months. In patients who received ramucirumab (10 mg/kg), pemetrexed (500 mg/m²) plus carboplatin (AUC=6) or cisplatin (75 mg/m²) once every three weeks, the median PFS was improved to 6.3 months (hazard ratio = 0.48; 90% CI; 0.31-0.74).

Ramucirumab was also studied in combination with paclitaxel and carboplatin as first-line therapy in patients with advanced NSCLC. Forty patients received ramucirumab (10 mg/kg), paclitaxel (200mg/m²), and carboplatin (AUC=6) on day one of a three-week cycle for up to six cycles, followed by maintenance ramucirumab.

The overall disease control rate (complete response + partial response + stable disease) reached 90% and PFS at six months was 59.0% (95% CI; 41.3-72.9). In this analysis, the median PFS was 7.85 months.

The REVEL lung cancer trial is the third positive phase III study of ramucirumab across multiple tumor types. The first, which studied ramucirumab in gastric cancer as a single agent, is the basis for initial regulatory submissions in the United States and Europe. The second studied ramucirumab in gastric cancer in combination with paclitaxel and is planned for regulatory submission in 2014.

Top-line results for phase III trials of ramucirumab in hepatocellular and colorectal cancer are expected later this year.