WASHINGTON —The FDA approved ramucirumab (Cyramza) in combination with erlotinib as first-line treatment for patients with untreated metastatic, epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).
NSCLC makes up the vast majority of lung cancer cases, and approximately 15% of patients who have NSCLC also have an EGFR mutation. Ramucirumab, a vascular EGFR 2 antagonist, in combination with erlotinib, an EGFR-targeting tyrosine kinase inhibitor, is specifically indicated for patient’s whose metastatic NSCLC has EGFR exon 19 deletions or exon 21 mutations.
This is “the first and only FDA-approved anti-VEGFR/EGFR TKI combination therapy for metastatic EGFR-mutated NSCLC,” ramucirumab’s manufacturer, Eli Lilly, wrote in a company press release.
According to the manufacturer, this approval is based on results from the global, randomized, placebo-controlled phase III RELAY trial that compared ramucirumab plus erlotinib versus placebo plus erlotinib in 449 patients with metastatic, EGFR-mutated NSCLC in North America, Europe, and Asia. The trial’s primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (OOR), duration of response (DoR), and overall survival (OS). Results from the RELAY trial were published in The Lancet in Dec. 2019.
“On the primary endpoint of investigator-assessed PFS, [ramucirumab] plus erlotinib (N=224) demonstrated statistically significant and clinically meaningful improvement in median PFS… by seven months compared to placebo plus erlotinib (n=225) (19.4 months in the [ramucirumab]-containing arm compared to 12.4 months in the placebo-containing arm [HR=0.59; 95% CI, 0.46, 0.76; P<0.0001]),” the manufacturer wrote. “The PFS treatment effect was consistent across exon 19 and exon 21 subgroups. At the time of the final analysis of PFS, OS data were not mature as only 26 percent of planned events for the final analysis had occurred (HR=0.83, 95% CI: 0.53, 1.30). A final OS analysis is planned when at least 300 events have occurred.”
The manufacturer noted that this was the second positive phase III trial of ramucirumab in metastatic NSCLC — the first was REVEL, which assessed ramucirumab plus docetaxel to treat patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy. The drug gained FDA-approval for this indication in Jan. 2015.
The most common adverse effects associated with treatment with combination ramucirumab/erlotinib (incidence rate ≥30%) were infections, hypertension, stomatitis, proteinuria, alopecia, and epistaxis — the most common laboratory abnormalities (incidence rate ≥30%) were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, and neutropenia.
Also, according to the prescribing information for ramucirumab, the drug may increase the risk of hemorrhage, gastrointestinal hemorrhage, and gastrointestinal perforations, which can be fatal. Patients should permanently discontinue treatment with ramucirumab if they experience any of these events.
Ramucirumab can also cause impaired wound healing — the drug should be withheld for 28 days prior to elective surgery and should not be administered for at least 2 weeks following major surgery. The drug can also cause arterial thromboembolic events, worsening of pre-existing hepatic impairment, posterior reversible encephalopathy syndrome, and thyroid dysfunction. The drug can also potentially harm a developing fetus.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 24
Topic ID: 78,24,730,24,192,725,65