Publication

Article

Oncology & Biotech News

July 2011
Volume5
Issue 7

MetMAb Plus Erlotinib Improves Survival for Patients With MET-Positive NSCLC

Add-on therapy with an inhibitor of the MET signaling pathway significantly improved PFS and OS in patients with MET-positive NSCLC confirmed by immunohistochemistry.

MetMAb pathway inhibition

Add-on therapy with an inhibitor of the MET signaling pathway significantly improved progression- free survival and overall survival (OS) in patients with MET-positive non—small cell lung cancer (NSCLC) confirmed by immunohistochemistry (IHC), according to final trial results presented in June at the ASCO meeting.

Patients treated with MetMAb (OAM4558g) plus erlotinib had a median OS of 12.6 months compared with 4.6 months for patients who received erlotinib plus placebo. The median PFS increased twofold with MetMAb (3.0 vs 1.5 mo).

In the overall analysis, patients treated with Met- MAb lived no longer than those in the placebo group. However, more than half of the patients in the trial had MET-positive tumors, said lead study author David Spigel, MD, a medical oncologist at Sarah Cannon Research Institute in Nashville, Tennessee.

“The combination of MetMAb and erlotinib leads to improved outcomes in MET-diagnosticpositive patients,” he said. “The effect was not driven by key subpopulations or imbalances in prognostic characteristics.”

“Outcomes in the diagnostic [MET-positive] subpopulations highlight the importance of diagnostic development,” said Spigel.

Multiple types of tumors exhibit MET pathway activation, which is associated with MET amplification, mutation, or overexpression. MET expression is associated with worse prognosis in several cancers, including NSCLC, and MET activation has been implicated in resistance to epidermal growth factor receptor (EGFR) inhibitors (eg, erlotinib) in patients with activating EGFR mutations.

MetMAb inhibits human growth factor—mediated stimulation of the MET pathway, and preclinical studies demonstrated activity against multiple tumors, including NSCLC, Spigel noted. In vitro and in vivo studies showed that inhibition of both EGFR and MET has more potent activity against tumor cells and models than inhibition of either pathway by itself, in part because MetMAb restored sensitivity to EGFR inhibition.

To examine the combination’s efficacy, investigators in a phase II trial enrolled patients with NSCLC previously treated with 1 or 2 lines of therapy. Patients were randomized to erlotinib 150 mg/day plus MetMAb 15 mg/kg every 3 weeks or placebo. Treatment continued to progression, at which time patients in the placebo arm could cross over to MetMAb.

erlotinib (Tarceva) 150 mg tablets

As part of the protocol, all patients underwent IHC assessment for MET status. MET-diagnosticpositive was defined as ≥50% of tumor cells with moderate or strong staining intensity. Of 128 patients enrolled, 93% had tissue samples adequate for evaluation by IHC. Additionally, MET status was assessed by fluorescence in situ hybridization (FISH) in 75% of evaluable specimens, and a FISH-positive result was defined as ≥5 copies.

The primary endpoint was PFS, and OS was a secondary endpoint. As reported last year at the European Society of Medical Oncology meeting, the addition of MetMAb did not improve PFS in the overall analysis. In fact, the placebo arm had a median PFS of 2.6 months compared with 2.2 months for the MetMAb arm. OS hinted at an advantage for MetMAb (8.9 vs 7.4 mo) but did not achieve statistical significance.

A prespecified subgroup analysis comprised 65 patients who were MET-diagnostic-positive by IHC and 19 patients who were positive by FISH. Among patients who were IHC-positive, treatment with MetMAb was associated with a 53% reduction in the hazard for progression (P = .01) and a 63% reduction in the survival hazard (P = .002). The FISH-positive subgroup had a 53% reduction in the survival hazard when treated with MetMAb, but the effect did not achieve statistical significance (P = .19).

On the basis of the results, a phase III trial has been planned, and accrual is expected to begin later this year, said Spigel.

Spigel DR, Ervin TJ, Ramlau R, et al. Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. J Clin Oncol. 2011;29(suppl; abstr 7505).

Newsletter

Stay up to date on the most recent and practice-changing oncology data

Latest CME

View All
Tumor Board: Expert Insights on Managing Classical 𝘌𝘎𝘍𝘙 Mutations, 𝘌𝘎𝘍𝘙 Exon 20 Insertions, and Atypical 𝘌𝘎𝘍𝘙 Mutations in Metastatic NSCLC
Video

Tumor Board: Expert Insights on Managing Classical 𝘌𝘎𝘍𝘙 Mutations, 𝘌𝘎𝘍𝘙 Exon 20 Insertions, and Atypical 𝘌𝘎𝘍𝘙 Mutations in Metastatic NSCLC

Jun 6th 2025 - Jul 12th 2025

online-activity
Medical Crossfire®: Expert Perspectives on Targeting c-Met Overexpression and 𝘔𝘌𝘛 Genomic Alterations in NSCLC – Unveiling the Complexities of 𝘔𝘌𝘛 Dysregulation
Video

Medical Crossfire®: Expert Perspectives on Targeting c-Met Overexpression and 𝘔𝘌𝘛 Genomic Alterations in NSCLC – Unveiling the Complexities of 𝘔𝘌𝘛 Dysregulation

Jun 6th 2025 - Jul 12th 2025

online-activity
Evolving Treatment Strategies in Pancreatic Cancer: Current Standards, Emerging Targets, and the Role of Molecular Testing
Video

Evolving Treatment Strategies in Pancreatic Cancer: Current Standards, Emerging Targets, and the Role of Molecular Testing

Jun 5th 2025 - Jul 12th 2025

online-activity