RELAY: Ramucirumab–erlotinib a potential first-line option for EGFR-mutated NSCLC
medwireNews: Combining erlotinib with ramucirumab significantly improves the progression-free survival (PFS) of untreated patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC), suggest phase III results presented at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA.
In the double-blind RELAY trial, median PFS was 19.4 months for the 224 participants who were randomly assigned to receive ramucirumab 10 mg/kg every 2 weeks in addition to erlotinib 150 mg/day for stage IV disease.
This was significantly higher than the median of 12.4 months for the 225 patients who instead received placebo plus erlotinib, and equated to a hazard ratio for progression or death of 0.591 in favor of combination therapy with the VEGFR2 antagonist ramucirumab plus the EGFR–tyrosine kinase inhibitor erlotinib.
This PFS benefit appeared not to be driven by an improvement in the objective response rate, which was similar in the ramucirumab and placebo arms (76 vs 75%), but rather by a significantly longer duration of response, at a median of 18.0 versus 11.0 months.
All participants either had the EGFR exon 19 deletion or the exon 21 L858R mutation, and there was no difference in PFS results by mutation type. Indeed, presenting author Kazuhiko Nakagawa (Kindai University Hospital, Osaka, Japan) noted that most subgroups appeared to derive a PFS advantage from the addition of ramucirumab to erlotinib.
Overall survival data were immature at data cutoff for this analysis, which was conducted at a median follow-up of 20.7 months, but at this stage there was no significant difference between treatment groups.
However, the presenter pointed out that the hazard ratio for the exploratory endpoint of PFS2 – defined as the time from randomization to progression after a subsequent therapy – significantly favored the ramucirumab arm, at 0.69, suggesting “the possibility of overall survival benefit.”
The rate of treatment-emergent adverse events (TEAEs) of at least grade 3 was higher among ramucirumab- than placebo-treated patients, at 72% and 54%, respectively, but a comparable 13% and 11% discontinued all study drugs due to TEAEs.
Twenty-four percent of patients in the combination arm experienced grade 3 hypertension, compared with 5% of those in the placebo arm, but there were no incidences of grade 4 or 5 hypertension in either group.
Nakagawa concluded that when approved by the regulatory authorities, the RELAY regimen of ramucirumab plus erlotinib would be “a new treatment option for initial treatment of EGFR-mutated metastatic NSCLC.”
Discussant Maurice Pérol (Léon Bérard Cancer Center, Lyon, France) described the trial as “well designed,” but commented that osimertinib, which is the new standard of care in this patient population, “should have been the control arm.”
He noted that although the median PFS and duration of response for ramucirumab–erlotinib were similar to those observed with osimertinib in the FLAURA trial, there are key differences between the studies, such as the exclusion of patients with brain metastases and a higher proportion of participants with a performance status of 0 in RELAY (52 vs 40% in FLAURA).
And in a comment to medwireNews, Medicine Matters oncology Advisory Board member Ross Camidge (University of Colorado Cancer Center, Aurora, USA) questioned the relevance of the trial results given that erlotinib is no longer the preferential agent for first-line treatment in these patients, having been superseded by osimertinib.
Camidge also highlighted that the RELAY regimen involves an intravenous infusion of ramucirumab every 2 weeks, instead of every 3 weeks as is usual for the drug in NSCLC, which puts patients on “a very short tether”.
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