Stephen Leong, MD
STEPHEN LEONG, MD, of the University of Colorado Comprehensive Cancer Center, Aurora, discussed the RAINFALL findings at the symposium, commenting, “The study did meet its primary endpoint of progression-free survival; however, it was disappointing not to see a benefit in overall survival or response rate.”
He maintained that while progression-free survival was improved, the median “was not that impressive…. The median reflects the 50th percentile, which is where the two curves actually came close together,” he said. The hazard ratio, on the other hand, is a broader evaluation “and is probably the more reliable result,” he maintained.
Previous outcomes in the second-line setting were more favorable for ramucirumab (Cyramza), showing hazard ratios for progression-free survival of 0.483 and 0.635. “This study did not have the same magnitude of benefit,” he observed.
Patients who received ramucirumab upon disease progression did appear to derive some benefit, he continued. “But, of note, only 50% of patients actually got second-line therapy, and even more interestingly, only 12% got ramucirumab, which is approved in the United States for second-line therapy.”
Cost and Biomarker Issues
OF MOST CONCERN, Dr. Leong emphasized, is the benefit translated into an average prolongation of remission of just 9 days. This has to be considered in the context of the high cost of the drug, he said, which was given for about 19 weeks to the average patient in this trial.
“In the United States, the drug cost (excluding infusion costs) for a 70-kg man is $7,457. Assuming the patient has no treatment delays, we estimate 12 treatments at a cost of more than $90,000,” he said.
Biomarker analyses are needed to try to identify patients who might benefit from this agent, he added. While correlative analyses have not yet been reported for RAINFALL, they have been done in other ramucirumab studies. In both REGARD and RAINBOW, no relevant biomarker was identified. However, in the RAISE study in colorectal cancer, serum vascular endothelial growth factor (VEGF)-D levels appeared to be associated with overall survival.1 In a study conducted in Korean gastric cancer patients, circulating angiogenic factors of VEGF receptor 2 and neurophilin were predictive of response.2
The bottom line, Dr. Leong concluded, is that ramucirumab will not receive approval from the U.S. Food and Drug Administration for a first-line indication; in fact, the manufacturer has said they will not pursue this, he added.
“Ramucirumab will not replace the current standard of care, which is a doublet or triplet with a fluorouracil or platinum backbone,” he said. “Will the [National Comprehensive Cancer Network] add ramucirumab to its recommendations for the first-line setting? That will be debated shortly.” ■
DISCLOSURE: Dr. Leong’s institution has received research funding from Eli Lilly.
1. Tabernero J, Hozak RR, Yoshino T, et al: Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Ann Oncol. December 7, 2017 (early release online).
2. Lim S, Heo S, Kim T, et al: Predictive biomarkers to ramucirumab in Asian metastatic gastric cancer patients: Circulating angiogenic factors of VeGFr2 and neurophilin are predictive to ramucirumab efficacy in Asian recurrent/ metastatic gastric cancer patients. 2016 ESMO Congress. Abstract 663P. Presented October 8, 2016.
BASED ON EFFICACY seen in the second-line setting for the treatment of metastatic gastric or gastroesophageal junction adenocarcinoma, ramucirumab (Cyramza) was evaluated as first-line therapy in the international phase III RAINFALL trial. Although the study met its primary endpoint, with a 25%...