A combination of ramucirumab (Cyramza?; Eli Lilly and Company, Indianapolis, IN 46285), a new anti-angiogenesis drug with standard docetaxel chemotherapy (Taxotere?; Sanofi, Bridgewater, NJ 08807) extends overall survival for patients who have a relapse after initial treatment compared to docetaxel plus placebo. This is the conclusion of drawn from research results of the REVEL Phase III study, which was supported by ImClone and presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held May 30 – June 3, 2014 in Chicago, Ill. The REVEL Study 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 or NSCLC.
Lung cancer is the leading cause of cancer death in the U.S. and most other countries, and NSCLC accounts for 85% of all lung cancer cases. It is estimated that approximately half of NSCLC patients are receiving treatment in the second-line 
setting. Despite currently available therapies, there continues to be a need for new second-line treatment options for patients with NSCLC.
For patients with stage IV non-small cell lung cancer (NSCLC) who have a relapse after initial treatment compared to docetaxel plus placebo, a combination of a new anti-angiogenesis drug and standard docetaxel chemotherapy extends overall survival. The median overall survival was 10.5 months in the ramucirumab arm compared to 9.1 months in the placebo arm.
?This is the first treatment in approximately a decade to improve the outcome of patients in the second-line setting,? explained lead investigator and study author Maurice P?rol, MD, Head of Thoracic Oncology at Cancer Research Center of Lyon(CRCL) in Lyon, France. ?The survival improvement is significant because patients with advanced NSCLC typically have a very short survival time following second-line therapy.?
“In the REVEL study, ramucirumab demonstrated statistically significant improvement across multiple efficacy endpoints including overall survival (OS), progression-free survival (PFS) and overall response rate. The improvement of overall survival and progression-free survival on the ramucirumab-plus-docetaxel arm was also consistent across the majority of subgroups including histology,” Perol further noted. “Overall, these results are very encouraging for those of us who treat lung cancer patients.”
Ramucirumab is an effective targeted agent when added to chemotherapy… It will be a significant benefit to those patients whose cancer progresses following initial chemotherapy…
Ramucirumab is a recombinant monoclonal antibody of the IgG1 class that specifically targets and binds to a protein called vascular endothelial growth factor receptor-2 (VEGFR-2), blocking the activity of the receptor and, as a result, blocking growth of new blood vessels in the tumor (angiogenesis). No other approved anti-angiogenesis drugs are available in the second-line setting for advanced NSCLC, and currently ramucirumab is approved only for advanced gastric cancer treatment.
Large unmet need
There is a large unmet medical need in the second-line treatment of advanced NSCLC, as all patients eventually experience a relapse following initial therapy.
Approved second-line therapies for advanced NSCLC include docetaxel, erlotinib, and pemetrexed (for non-squamous NSCLC only), though clinical outcomes remain poor, with tumor shrinkage rates around 10% and median overall survival ranging between seven and nine months.
In the study, 1,253 patients with stage IV NSCLC (26% had the squamous subtype) that had progressed despite standard platinum-based therapy were randomly assigned to treatment with ramucirumab plus docetaxel or placebo plus docetaxel.
The addition of ramucirumab improved the efficacy of second-line docetaxel therapy ? 22.9% of patients experienced tumor shrinkage in the ramucirumab arm compared to 13.6% in the placebo arm. The median overall and progression-free survival periods were 10.5 and 4.5 months in the ramucirumab plus docetaxel arm vs. 9.1 and 3 months in the placebo plus docetaxel arm, respectively. The survival benefits were consistent in the major subgroups of patients, including squamous and non-squamous subtypes, suggesting that this therapy could be suitable for all major subtypes of NSCLC. The safety profile was as expected for an anti-VEGFR agent in combination with docetaxel, with no increase in the rate of pulmonary hemorrhage (acute bleeding from the lung).
Adverse Events
The most common ( > 5% incidence) Grade > /=3 adverse events occurring more frequently in patients on the ramucirumabarm were neutropenia (48.8% vs. 39.8%), febrile neutropenia (15.9% vs. 10.0%), fatigue (14.0% vs 10.5%), leukopenia (13.7% vs. 12.5%), and hypertension (5.6% vs. 2.1%). Grade 5 adverse events were comparable between arms (5.4% vs. 5.8%). Patients on the ramucirumabarm experienced more bleeding/hemorrhage events (all grade) (28.9 % vs 15.2%) but the rate of Grade > /=3 bleeding / hemorrhage events were similar between arms (2.4% vs 2.3%).
Expanding Treatment Options
Commenting on the study results, Gregory A. Masters, MD, ASCO Expert, Director, Medical Oncology Fellowship and lung cancer specialist at the Christiana Care’s Helen F. Graham Cancer Centerin Newark, DE 19713, noted: ?This study expands the treatment options for patients with recurrent or refractory non-small cell lung cancer. Ramucirumab is an effective targeted agent when added to chemotherapy, with low toxicity. This will be a significant benefit to those patients whose cancer progresses following initial chemotherapy.?
For more information:
[1] P?rol M, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, G?ksel T, Park K, Kowalyszyn RD, 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. 2014 ASCO Annual Meeting, Oral Abstract Session, Monday June 2, 3:00 PM to 6:00 PM, Abstract No: LBA8006^ Citation: J Clin Oncol 32:5s, 2014 (suppl; abstr LBA8006^)[Abstract]
[2] Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. The Lancet, Lancet. 2014 June 2, Early Online Publication. [Article]
Photo: Maurice Perol M.D., speaks at the 50th Annual Meeting of the American Society of Clinical Oncology. Photo Courtesy:? ASCO/Phil McCarten.
Copyright ? 2014 InPress Media Group/Sunvalley Communication.
All rights reserved. Republication or redistribution of InPress Media Group/Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent ofInPress Media Group/Sunvalley Communication. InPress Media Group/Sunvalley Communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco’Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.
