Dual EGFR, VEGF Blockade Improves PFS in Patients With Treatment-Naive, EFGR-Mutated NSCLC

By Cameron Kelsall, /alert Contributor
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Treatment with the monoclonal antibody ramucirumab, in combination with erlotinib, significantly improved progression-free survival (PFS) when compared with placebo in patients with untreated, EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to results of the phase 3 RELAY trial published in The Lancet.

NSCLC accounts for up to 85% of worldwide lung cancers, the majority of which are diagnosed at an advanced stage. EGFR mutations are present in up to 20% of white patients with NSCLC and up to 60% of Asian patients.

Stethoscope. Source: Getty

Although previous research has supported the dual blockade of EGFR and VEGF pathways for patients with EGFR-mutated advanced NSCLC, the treatment strategy remains uncommon in clinical practice.

Kazuhiko Nakagawa, MD, PhD, professor of medical oncology at Kindai University in Osaka, Japan, and colleagues sought to dual blockade with ramucirumab and erlotinib, a standard-of-care EGFR tyrosine kinase inhibitor, with erlotinib plus placebo.

The RELAY clinical trial recruited adult patients with untreated stage IV NSCLC and an EGFR exon 19 deletion or exon 21 substitution mutation. Patients were randomly assigned to daily oral erlotinib (150 mg), plus biweekly intravenous ramucirumab (10 mg/kg) or placebo.

PFS in the intent-to-treat population served as the study’s primary endpoint, with safety assessments conducted in all patients who received at least one treatment dose.

The intent-to-treat population included data from 449 patients assigned to ramucirumab (n = 224) or placebo (n = 225). Median age was similar in both study arms (ramucirumab, 65 years; placebo, 64 years). In total, 54% of patients assigned ramucirumab and 49% of patients assigned placebo were aged 65 years or older.

Median follow-up was 20.7 months (interquartile range, 15.8-27.2).

At the time of reporting, 29% (n = 64) of patients assigned ramucirumab and 19% (n = 43) of patients assigned placebo remained on treatment. Disease progression or death was observed in 48% (n = 108) of patients assigned ramucirumab and 65% (n = 165) of patients assigned placebo.

Investigator-assessed PFS favored treatment with ramucirumab when compared with placebo (median, 19.4 months vs. 12.4 months; stratified hazard ratio [HR], 0.59; 95% CI, 0.46-0.76; P < .0001).

The researchers reported that overall survival (OS) data were immature at the time of data cutoff, with median OS not reached in either treatment arm.

Grade 3 or grade 4 treatment-related adverse events occurred in 72% (n = 159) of patients assigned ramucirumab and 54% (n = 121) of patients assigned placebo.

Among patients assigned ramucirumab, the most common treatment-emergent adverse events were grade 3 hypertension (24%) and dermatitis acneiform (15%). The most common adverse events in the placebo arm were dermatitis acneiform (9%) and alanine aminotransferase (8%).

Serious adverse events occurred in 29% (n = 65) of patients assigned ramucirumab and 21% (n = 47) of patients assigned placebo.

Among patients assigned ramucirumab, the most common serious adverse events of any grade were pneumonia (3%), cellulitis (2%) and pneumothorax (2%). Among patients assigned placebo, the most common serious adverse events were pyrexia (2%) and pneumothorax (1%).

According to the researchers, the safety profiles observed with the ramucirumab/erlotinib combination aligned with the known profiles of each individual compound in patients with advanced lung cancer.

One patient assigned ramucirumab died while receiving treatment due to hemothorax following thoracic drainage for pleural empyema. The death was deemed study related.

“In conclusion, ramucirumab plus erlotinib provided superior PFS versus placebo plus erlotinib in first-line metastatic EGFR-mutated NSCLC,” the researchers wrote. “The RELAY regimen is therefore a viable new treatment option for the initial treatment of patients with metastatic EGFR-mutated NSCLC.”


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