Ramucirumab Combination Improves OS and PFS in NSCLC

March 20, 2014
Christina Izzo

Evidence-Based Oncology, November/December 2013, Volume 19, Issue SP13

The second-line administration

of ramucirumab in combination

with docetaxel has shown a statistically

significant improvement in

overall survival (OS) and progressionfree

survival (PFS), compared with placebo

plus docetaxel, in patients with

non-small cell lung cancer (NSCLC),

according to Eli Lilly and Company, the

developer of the agent.

The phase 3 REVEL randomized

double-blind trial compared ramucirumab

and docetaxel with 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,

with both squamous and nonsquamous

NSCLC, were enrolled across 26


“We are pleased with these phase

3 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

3 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 with 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, a fully human monoclonal

antibody, targets vascular endothelial

growth factor receptor-2. It is

designed to directly inhibit angiogenesis,

a process by which blood vessels

supply blood to tumors.

In an open-label phase 2 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 3 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 3

weeks, the median PFS was improved

to 6.3 months (hazard ratio = 0.48; 90%

confidence interval [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 1 of a 3-week cycle

for up to 6 cycles, followed by maintenance


The overall disease control rate

(complete response + partial response

+ stable disease) reached 90% and PFS

at 6 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 3 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 study evaluated ramucirumab

in gastric cancer in combination

with paclitaxel and is scheduled

for regulatory submission in 2014.

Top-line results for phase 3 trials of

ramucirumab in hepatocellular and

colorectal cancer are expected later

this year.

Ramucirumab Combination Improves OS and PFS in NSCLC