Cyramza® (ramucirumab): RELAY-studien

Cyramza® (ramucirumab): The RELAY study

Cyramza in combination with erlotinib is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations.

Study Design

The RELAY trial was a phase 3, global, multicenter, randomized, double-blind, placebo-controlled trial in patients (N=449) with previously untreated EGFR mutation-positive, metastatic NSCLC. All patients had an EGFR mutation of exon 19 deletion or exon 21 L858R and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by sex, region, EGFR mutation type, and EGFR testing method) to receive treatment with erlotinib (150 mg/day) plus ramucirumab (10 mg/kg every 2 weeks; n=224) or placebo (every 2 weeks; n=225) until disease progression or unacceptable toxicity.¹

Efficacy Results

Patients treated with ramucirumab plus erlotinib had a significantly longer median PFS (investigator-assessed) than patients treated with placebo plus erlotinib (19.4 months vs 12.4 months; HR=0.59; 95% CI: 0.46-0.76; p<.0001). A consistent PFS benefit was also observed in an independent, blinded central review (HR=0.671; 95% CI: 0.518-0.869; p=.0022) as well as in both EGFR mutation types (exon 19 deletion [HR=0.65; 95% CI: 0.47-0.90; p=.0098] and exon 21 L858R [HR=0.62; 95% CI: 0.44-0.87; p=.0060]).¹

The median interim OS and PFS2 have not yet been reached for either treatment group.¹

Efficacy endpoint results are summarized in Table 1.

Table 1. Efficacy Endpoint Results¹

Abbreviations: CR = completed response; DCR = disease control rate; DOR = duration of response; ERL = erlotinib; HR = hazard ratio; ORR = objective response rate; PBO = placebo; PD = progressive disease; PFS = progression-free survival; PR = partial response; RAM = ramucirumab; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease.

^a Investigator-assessed. A consistent PFS benefit was observed in the sensitivity analysis of PFS by independent, blinded central review (HR=0.671; 95% CI: 0.518-0.869; p=.0022).

^b Response rate assessed using RECIST 1.1 at baseline, every 6 weeks for the first 72 weeks, and then every 12 weeks thereafter.

^c Treatment difference, CR or PR, was estimated with the stratified method of Miettinen and Nurminen.

^d Unstratified p value.

Safety Results

In the ramucirumab plus erlotinib group compared to the placebo plus erlotinib group

• grade ≥3 TEAEs were reported in 72% of patients vs 54% of patients, and

• any grade TE-SAE were reported in 29% of patients vs 21% of patients.¹

Treatment-emergent adverse events that occurred in ≥20% of patients are summarized in Table 2.

Table 2. Treatment-Emergent Adverse Events Occurring in ≥20% of Patients^1,2

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; ERL = erlotinib; ILD = interstitial lung disease; PBO = placebo; RAM = ramucirumab; TEAE = treatment-emergent adverse event.

^a No deaths were reported due to TEAEs occurring in at least 20% of participants; 1 death occurred on study and was because of a pulmonary hemorrhage event of hemothorax; 1 patient in the placebo group had a fatal event of ILD more than 30 days after treatment discontinuation.

^b Includes 2 patients (1%) with grade 4 events.

^c Includes 3 patients (1%) with grade 4 events.

^d Includes 1 patient (<1%) with a grade 4 event.

References

1. Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669. https://doi.org/10.1016/S1470-2045(19)30634-5

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

HR = hazard ratio

NSCLC = non-small cell lung cancer

OS = overall survival

PFS = progression-free survival

PFS2 = time from randomization to 2nd disease progression (defined as objective radiological or symptomatic progression after start of additional systematic anticancer treatment), or death from any cause, whichever comes first

PS = performance status

TEAE = treatment-emergent adverse event

TE-SAE = treatment-emergent serious adverse events