FDA Approves Ramucirumab Plus Erlotinib for First-Line Treatment of Metastatic NSCLC

June 01, 2020

On May 29, 2020, the U.S. Food and Drug Administration (FDA) approved ramucirumab (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-ramucirumab-plus-erlotinib-first-line-metastatic-nsclc) (Cyramza®) in combination with erlotinib for first-line treatment of metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. 

FDA Approves Ramucirumab Plus Erlotinib for First-Line Treatment of Metastatic NSCLC

Efficacy was evaluated in a multinational, randomized, double-blind, placebo-controlled, multicenter study (RELAY; NCT02411448) in patients with previously untreated metastatic NSCLC whose tumors have EGFR exon 19 deletion or L858R substitution mutations. A total of 449 patients were randomized 1:1 to receive either ramucirumab 10 mg/kg or placebo every two weeks as an IV infusion, in combination with erlotinib 150 mg orally once daily, until disease progression or unacceptable toxicity. 

The major efficacy outcome measure was progression-free survival (PFS) as assessed by the investigator using response evaluation criteria in solid tumors 1.1. Additional efficacy outcome measures were overall survival (OS), overall response rate (ORR), and duration of response (DoR). Median PFS was 19.4 months in the ramucirumab plus erlotinib arm compared to 12.4 months in the placebo plus erlotinib arm (HR = 0.59; 95% CI = 0.46, 0.76; p < 0.0001). 

ORR was 76% in the ramucirumab plus erlotinib arm and 75% in the placebo plus erlotinib arm, with median DoR of 18.0 months and 11.1 months, respectively. At the time of the final PFS analysis, OS data were not mature because only 26% of the deaths required for the final analysis had occurred (HR = 0.83; 95% CI = 0.53, 1.30). 

The most common adverse reactions observed in ≥ 20% of patients treated with ramucirumab with erlotinib (≥ 2% higher than placebo with erlotinib) were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. The most common laboratory abnormalities identified in ≥ 20% of patients treated with ramucirumab (≥ 2% higher than placebo) were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, thrombocytopenia, neutropenia, increased alkaline phosphatase, and hypokalemia. 

The recommended dose of ramucirumab for metastatic NSCLC in combination with erlotinib is 10 mg/kg every two weeks. 

View full prescribing information for ramucirumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125477s034lbl.pdf)

This review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.   

For assistance with single-patient oncology investigational new drug applications, contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).   

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