Maurice Pérol, MD
Adding the VEGFR-2 inhibitor ramucirumab (Cyramza) to standard docetaxel improved overall survival (OS) by 1.4 months versus docetaxel alone in patients with advanced non–small cell lung cancer (NSCLC), according to data from the phase III REVEL trial presented at the 2014 ASCO Annual Meeting.
“The REVEL study is the first study in approximately a decade demonstrating an improvement in overall survival for patients treated in the second-line setting for advanced non–small cell lung cancer,” lead author Maurice Pérol, MD, head of Thoracic Oncology at Cancer Research Center of Lyon in France, said in a press briefing at ASCO.
Patients with advanced NSCLC who relapse have a median OS of only 7 to 9 months. Available treatments in the second-line setting include erlotinib, docetaxel, and pemetrexed (nonsquamous NSCLC only). If approved, ramucirumab would become the first antiangiogenesis agent in this setting.
The double-blind, phase III REVEL study involved 1253 patients with squamous (26.2%) and nonsquamous (73.8%) stage IV NSCLC (ECOG performance status ≤1). Accrual occurred between December 2010 and February 2013. All patients had disease progression during or after treatment with one platinum-based chemotherapy either with or without maintenance therapy. Prior bevacizumab (Avastin) treatment was allowed.
In a 1:1 randomization, patients were assigned to receive 75 mg/m2
of docetaxel combined with either 10 mg/kg of ramucirumab (n = 628) or placebo (n = 625) on day 1 of a 3-week cycle. Treatment was administered until disease progression or unacceptable toxicity. Patient characteristics were balanced between the treatment groups. OS was the primary endpoint, and secondary endpoints included progression-free survival (PFS) and overall response rate (ORR).
The study met its primary endpoint with median OS of 10.5 months in the ramucirumab arm versus 9.1 months in the placebo arm (HR = 0.857; 95% CI, 0.751-0.98; P
= .0235). The survival benefit was upheld across most patient subgroups, including both squamous and nonsquamous histology.
Median PFS was 4.5 months with the ramucirumab combination compared with 3 months in patients receiving docetaxel alone (HR = 0.762; P
<.0001). ORR was 22.9% and 13.6%, respectively (P
“The safety profile suggest[ed] minimal and manageable increased risk due to the addition of ramucirumab to docetaxel in second-line NSCLC,” said Pérol.
Grade ≥3 adverse events occurring in >5% of patients in the ramucirumab arm were neutropenia (34.9% vs 28.0% with docetaxel alone), febrile neutropenia (15.9% vs 10.0%), fatigue (11.3% vs 8.1%), leukopenia (8.5% vs 7.6%), hypertension (5.4% vs 1.9%), and pneumonia (5.1% vs 5.8%).
The percentage of deaths associated with AEs was comparable between the ramucirumab and control arms (5.4% vs. 5.8%). Rates of pulmonary hemorrhage were also similar: 2.1% vs 1.6% among all patients and 3.8% vs 2.4% in patients with squamous histology.
Commenting on the REVEL data, press briefing moderator Gregory Masters, MD, a medical oncologist at the Helen F. Graham Cancer Center, said, “It’s exciting to see progress in this disease, where the steps are small, but cumulative. We’re excited to have another agent that shows activity, especially in this very difficult-to-treat, second-line population in non–small cell lung cancer.”
In an interview with OncLive
, Suresh Ramalingam, professor of Hematology and Oncology at Emory University and the Winship Cancer Institute, commented on the next step with ramucirumab in NSCLC.
“The important additional things that need to be done are to see if there’s a biomarker that would select those patients that have a greater degree of benefit, rather than giving the drug to everybody. And that is an area actually where we have not had much success—in the angiogenesis axis, we have not had many good biomarkers, and that has been a hurdle for a number of these drugs.”
Ramucirumab is currently approved by the FDA for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma with disease progression during or following prior treatment with fluoropyrimidine- or platinum-containing chemotherapy. The drug was also examined in HER2-negative metastatic breast cancer, but failed to delay disease progression in a phase III trial.
The REVEL study was supported by ImClone, a subsidiary of Eli Lilly, which manufactures ramucirumab.
Pérol M, Ciuleanu TE, Arrieta O, et al. REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy. J Clin Oncol. 2014;32:5s (suppl; abstr LBA8006).
<<< View more from the 2014 ASCO Annual Meeting