Ramucirumab plus Erlotinib in the Treatment of Patients with NSCLC with EGFR Exon 19 or Exon 21 Mutations

First-line treatment with ramucirumab plus erlotinib in patients with EGFR-mutated metastatic NSCLC was associated with superior progression-free survival compared with erlotinib plus placebo.

The RELAY trial evaluated the efficacy and safety of first-line therapy with the EGFR tyrosine kinase inhibitor erlotinib together with either the human IgG VEGFR2 antagonist ramucirumab or placebo in patients with EGFR-mutated metastatic non–small-cell lung cancer (NSCLC).¹ To be eligible, patients had to present with untreated metastatic NSCLC with exon 19 deletion or L858R mutation and no evidence of central nervous system metastasis.¹ Patients were randomized to receive once-daily erlotinib 150 mg combined with ramucirumab 10 mg/kg every 2 weeks or once-daily erlotinib 150 mg plus placebo.¹ The study arms were stratified by EGFR mutation type (exon 19 deletion vs L858R mutation), EGFR mutation testing method (therascreen or Cobas vs others), gender, and geographic region (East Asia vs others).¹

The RELAY trial’s primary end point was investigator-assessed progression-free survival (PFS). Other end points included overall response rate, duration of response (DOR), time from randomization to progression after a subsequent therapy (PFS2), overall survival, safety, and rate of plasma T790M mutation using the Guardant next-generation sequencing test.¹

For the RELAY trial, 449 patients were randomized to 2 treatment arms that were well-balanced in terms of disease and demographic characteristics: Asian race (77%), female gender (63%), and exon 19 deletion (54%).¹ The combination of ramucirumab plus erlotinib was associated with significantly prolonged PFS (median, 19.4 months) compared with erlotinib plus placebo (12.4 months; P <.0001). The combination of ramucirumab plus erlotinib was also associated with longer DOR (median, 18.0 months) compared with erlotinib plus placebo (11.¹ months; P = .0003). Although the combination of ramucirumab plus erlotinib was also associated with longer PFS2 compared with erlotinib plus placebo, medians were not reached in either arm (P = .0325).¹

Treatment-emergent adverse events grade ≥3 were more common with ramucirumab plus erlotinib (72%) than with erlotinib plus placebo (54%).¹ This difference was largely accounted for by hypertension (24% vs 5%, no grade 4).¹ There was 1 treatment-related on-study death due to hemothorax in the ramucirumab plus erlotinib arm (none in the placebo arm).¹

In the RELAY study, researchers evaluated patient-reported outcomes as a part of the secondary outcome measures. The burden of patients’ disease-related symptoms was prospectively assessed by the Lung Cancer Symptom Scale (LCSS).² Mean LCSS scores were found to be similar for the 2 treatment arms across all study treatment visits, including the 30-day follow-up visit.²

Researchers concluded that first-line use of ramucirumab plus erlotinib was associated with superior PFS in patients with EGFR-mutated metastatic NSCLC compared with erlotinib plus placebo.¹ The combination treatment’s safety profile was consistent with previously published risks of the individual drugs.¹ Overall quality of life and symptom burden were the same with ramucirumab plus erlotinib compared with erlotinib plus placebo.²

References

1. Nakagawa K, et al. J Clin Oncol. 2019;37(suppl 15). Abstract 9000.
2. Yoh K, et al. Curr Med Res Opin. 2020;36:1667-1675.