Ramucirumab, Erlotinib Combo a Promising First-line EGFR-Mutated NSCLC Treatment

Ramucirumab (Cyramza, Eli Lilly), in combination with erlotinib, significantly improved progression-free survival (PFS) in first-line epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), according to results from a phase 3 study published in The Lancet Oncology.

Tyrosine kinase inhibitors (TKIs), including erlotinib, are the current standard of care for EGFR-mutated NSCLC, but many patients require several lines of treatment. Disease progression following acquired resistance to prior therapies remains a challenge for patients, according to the study authors.

The RELAY trial evaluated ramucirumab in combination with erlotinib compared with placebo in combination with erlotinib as a first-line therapy in 449 previously untreated patients with metastatic EGFR-mutated NSCLC.

According to the findings, ramucirumab plus erlotinib demonstrated a statistically significant and clinically meaningful improvement in median PFS by 7 months compared with placebo plus erlotinib (19.4 months with the ramucirumab-containing arm compared with 12.4 months with the placebo-containing arm [HR 0.59; 95% CI, 0.46-0.79; P=<0.0001]).

Additionally, the data showed improvements across all specified subgroups, such as patients with tumors that had exon 19 and 21 mutations, which are the most commonly found EGFR mutations in NSCLC tumors.

“Despite recent treatment advances in metastatic EGFR-mutated NSCLC, there is an ongoing unmet need for additional first-line treatment options and new treatment strategies,” lead trial investigator Edward Garon, MD, School of Medicine, University of California, said in a statement. “Therapeutic combinations are one such strategy to provide more options for patients that can potentially delay disease progression and the emergence of acquired resistance.”

The most common mechanism of acquired resistance to first-line treatment with EGFR-TKIs is the T790M mutation, according to Lilly. In the study, the rate of T790M mutations following disease progression was similar between treatment groups.

In terms of safety, the most common treatment-related grade ≥3 adverse events occurring at a rate of 5% or greater in the ramucirumab group were hypertension, dermatitis aceniform, and diarrhea.

Based on the phase 3 data, the authors concluded that “the RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC.”

Ramucirumab was also evaluated in combination with docetaxel compared with placebo plus docetaxel in the phase 3 REVEL study in patients with metastatic NSCLC whose cancer had progressed on or after prior platinum-based chemotherapy. In this study, the primary endpoint of overall survival was met, as well as key secondary endpoints of PFS and response rate.

References

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 randomized, double-blind, placebo-controlled. The Lancet Oncology. 2019. https://doi.org/10.1016/S1470-2045(19)30634-5

Lilly’s Cyramza (ramucirumab) phase 3 data in first-line EGFR-mutated non-small cell lung cancer published in The Lancet Oncology [news release]. Eli Lilly’s website. https://investor.lilly.com/news-releases/news-release-details/lillys-cyramzar-ramucirumab-phase-3-data-first-line-egfr-mutated. Accessed October 7, 2019.