Ramucirumab: Safety Data on Use in Patients with NSCLC in Combination with Docetaxel

Use in Treatment of Non-Small Cell Lung Cancer

Ramucirumab, in combination with

• docetaxel, is indicated for the treatment of patients with locally advanced or metastatic NSCLC with disease progression after platinum-based chemotherapy, or

• erlotinib, is indicated for the first-line treatment of patients with metastatic NSCLC with activating EGFR mutations.¹

Study Design

The REVEL trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with pathologically confirmed, squamous or nonsquamous, stage IV NSCLC with disease progression during or after 1 prior platinum-based chemotherapy. Prior treatment with bevacizumab and prior maintenance therapy were allowed and all patients had an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by sex, region, PS, and previous maintenance therapy) to receive treatment with ramucirumab (10 mg/kg every 3 weeks) plus docetaxel (75 mg/m² every 3 weeks) (n=628) or placebo plus docetaxel (75 mg/m² every 3 weeks) (n=625) until disease progression, unacceptable toxicity, withdrawal, or death.²

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.³

Safety

REVEL Study

The frequency and severity of adverse reactions that have been reported at an incidence rate of ≥5% in patients who received ramucirumab in combination with docetaxel in the REVEL study are summarized in Table 1.

Table 1. Adverse Reactions that Occurred at an Incidence Rate of ≥5% in Patients Who Received Ramucirumab in Combination With Docetaxel in the REVEL Trial^1,2

Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities.

RELAY Study

The frequency and severity of adverse reactions that have been reported at an incidence rate of ≥5% in patients who received ramucirumab in combination with erlotinib in the RELAY study are summarized in Table 2.

Table 2. Adverse Reactions that Occurred at an Incidence Rate of ≥5% in Patients who Received Ramucirumab in Combination with Erlotinib in the RELAY Trial^1,3

Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities; NA = not applicable. 

^a MedDRA preferred terms included anal hemorrhage, hemorrhoidal hemorrhage hematochezia, lower gastrointestinal hemorrhage, rectal hemorrhage, small intestinal hemorrhage, melena, duodenal ulcer hemorrhage, and upper gastrointestinal hemorrhage.

^b Infections include all preferred terms that are part of the System Organ Class Infections and Infestations. Most common (≥1%) grade ≥3 infections include pneumonia, cellulitis, paronychia, skin infection, and urinary tract infection.

^c MedDRA preferred terms included hemoptysis, laryngeal hemorrhage, hemothorax, and pulmonary hemorrhage.

^d Grade ≥3 does not exist in CTCAE.

References

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

2. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. http://dx.doi.org/10.1016/S0140-6736(14)60845-X

3. 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

Glossary

AE = adverse event

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

NSCLC = non-small cell lung cancer

PS = performance status