CHICAGO, IL—Second-line ramucirumab plus docetaxel significantly improved overall survival (OS), progression-free survival (PFS) and overall response rates (ORR) compared with docetaxel alone in patients with stage IV non-small cell lung cancer (NSCLC), results of the phase 3 REVEL study concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
“REVEL is the first study showing that addition of a novel agent to standard chemotherapy improves survival in [patients with] stage IV NSCLC with progression after platinum-based chemotherapy,” said Maurice Perol, MD, Head of Thoracic Oncology at the Léon-Bérard Cancer Centre, Lyon, France. Benefits were similar in patients with nonsquamous and squamous histology.
Ramucirumab, a human IgG1 monoclonal antibody that targets the extracellular domain of vascular endothelial growth factor receptor (VEGFR)-2, was approved as monotherapy by the Food and Drug Administration in April 2014 for the second-line treatment of advanced gastric cancer. Angiogenesis is a critical target in advanced NSCLC, he pointed out, with VEGF-A and VEGFR-2 axis as the primary angiogenic driver.
Between December 2010 and February 2013, the phase 3 REVEL study randomly assigned 1,253 patients to docetaxel 75 mg/m2 in combination with either ramucirumab 10 mg/kg (n = 628) or placebo (n = 625) on day 1 of a 21-day cycle every 3 weeks until disease progression, unacceptable toxicity, or death. The primary endpoint was OS; secondary endpoints included PFS and ORR.
In both arms, 66% of the patients were male; median age was 62 years in the ramucirumab arm and 61 years in the docetaxel-alone arm, and 83.8% and 80.5% were Caucasian, respectively. In the ramucirumab arm, 25.0% of the patients had squamous histology, as did 27.4% in the docetaxel-alone arm.
REVEL met its primary endpoint: the OS hazard ratio (HR) was 0.857 (95% CI: 0.751-0.98; P=0.0235); median OS was 10.5 months (range, 9.5-11.2 months) for ramucirumab plus docetaxel versus 9.1 months (range, 8.4-10.0 months) for docetaxel. Median OS was longer for ramucirumab plus docetaxel in most patient subgroups, including those with squamous (unstratified HR, 0.88) and nonsquamous (unstratified HR, 0.83) histology.
The HR for PFS was 0.762 (95% CI: 0.677-0.859, P<0.0001); median PFS was 4.5 months (range, 4.2-5.4 months) for ramucirumab plus docetaxel versus 3.0 months (range, 2.8-3.9 months) for docetaxel alone.
The ORR was 22.9% (95% CI: 19.7%-26.4%) for ramucirumab plus docetaxel versus 13.6% (95% CI: 11.0%-16.5%) for docetaxel (P < 0.001). In the ramucirumab-plus-docetaxel arm, three patients had a complete response (CR); 141, a partial response (PR); and 258, stable disease (SD), for a disease control rate (DCR) of 64.0% (95% CI: 60.1%-67.8, P < 0.001). In the docetaxel-alone arm, two patients had a CR; 83, a PR; and 244, SD, for a DCR of 52.6% (95% CI: 48.6%-56.5%, P < 0.001).
Grade 3 or 4 adverse events (AEs) occurring in greater than 5% of patients on ramucirumab plus docetaxel included neutropenia (48.8% vs. 39.8% for docetaxel alone), febrile neutropenia (15.9% vs. 10.0%), and fatigue (14.0% vs. 10.5%).
Grade 5 AEs were comparable between arms, with 34 deaths (5.4%) in the ramucirumab-plus-docetaxel arm and 35 deaths (5.7%) on the docetaxel-alone arm; of these, 15 (2.4%) and 9 (1.5%) were related to any study drug. Any grade pulmonary hemorrhage was 2.0% versus 1.6%, respectively.
The REVEL study results were published in The Lancet at the conclusion of Dr. Perol’s presentation.
- Perol M, Ciuleanu TE, Arrieta O et al. Abstract LBA8006. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.