Ramucirumab Plus Osimertinib in NSCLC: Final Analysis of Phase I Trial
Posted: Tuesday, December 15, 2020
According to the final analysis of the phase I JVDL trial, presented in Clinical Cancer Research, a combination treatment of the VEGFR2-directed antibody ramucirumab plus the EGFR tyrosine kinase inhibitor osimertinib may be active and safe for some patients with non–small cell lung cancer (NSCLC). The study sought to determine whether the addition of ramucirumab may improve the clinical activity of osimertinib, resistance to which is universally developed.
“These findings, together with the recent report of the [progression-free survival] benefit of ramucirumab plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC, indicate the dual targeting of EGFR and VEGFR pathways may be a promising new treatment strategy for EGFR-mutant advanced NSCLC,” concluded David Planchard, MD, PhD, of Gustave Roussy, France, and colleagues.
The study included 25 patients with EGFR T790M–positive NSCLC who had experienced disease progression after EGFR tyrosine kinase inhibitor treatment but who had not been exposed to a third-generation agent. All participants received oral osimertinib daily and intravenous ramucirumab biweekly until disease progression or treatment discontinuation. At a median follow-up of 25 months, five patients remained on treatment.
The objective response rate was 76%, with a median response duration of 13.4 months, and the median progression-free survival was 11 months. Patients with or without central nervous system metastasis both experienced treatment efficacy (objective response rates of 60% and 87% and progression-free survival of 10.9 and 14.7 months, respectively). Unlike an on-treatment loss of T790M, an on-treatment loss of EGFR exon 19 deletion or L858R mutation seemed to be associated with prolonged progression-free survival.
Safety outcomes were comparable for patients with or without central nervous system metastasis. Decreased platelet counts (16%) and hypertension (8%) were common treatment-related adverse events of at least grade 3. One patient experienced a grade 5 subdural hemorrhage.
Disclosure: For full disclosures of study authors, visit clincancerres.aacrjournals.org.