Related Experiment Video

Updated: May 13, 2026

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
09:11

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Published on: May 24, 2024

[A new drug in thoracic oncology: MetMab (onartuzumab)]

É Giroux Leprieur1

  • 1Service de pneumologie et oncologie thoracique, université Versailles-Saint-Quentin-en-Yvelines, hôpital Ambroise-Paré, 9, avenue Charles-de-Gaulle, 92100 Boulogne-Billancourt, France. etienne.giroux-leprieur@apr.aphp.fr

Revue De Pneumologie Clinique
|March 13, 2013
PubMed

Insights

Adding MetMab to erlotinib significantly improved progression-free and overall survival in advanced non-small cell lung cancer (NSCLC) patients with Met overexpression. This combination therapy shows promise for treating resistant NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Trials

Background:

  • The Met pathway is frequently activated in solid cancers, contributing to acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with EGFR mutations.
  • Met amplification occurs in 5-20% of NSCLC cases resistant to TKIs.
  • MetMab (onartuzumab) is a humanized anti-Met antibody designed to block Met receptor signaling by preventing ligand binding.

Purpose of the Study:

  • To evaluate the efficacy and safety of combining erlotinib with MetMab in patients with advanced NSCLC.
  • To assess the impact of Met overexpression, identified by immunohistochemistry (IHC), on treatment outcomes.

Main Methods:

  • A randomized phase II trial involving 128 patients with advanced NSCLC receiving second or third-line treatment.
  • Patients were randomized to receive either erlotinib plus placebo or erlotinib plus MetMab (15mg/kg IV every 3 weeks) until disease progression or toxicity.
  • Met expression levels were assessed using immunohistochemistry (IHC).

Main Results:

  • In patients with Met overexpression (positive IHC), the erlotinib+MetMab combination resulted in a two-fold longer progression-free survival (PFS) and a three-fold longer overall survival (OS) compared to the control arm.
  • Median PFS was 2.9 months vs. 1.5 months (HR=0.53; P=0.04) and median OS was 12.6 months vs. 3.8 months (HR=0.37; P=0.002) for Met-positive patients.
  • In patients with negative IHC for Met, the combination therapy showed no benefit and potentially worse outcomes.
  • MetMab demonstrated a favorable toxicity profile, with peripheral edema being the most common adverse event, typically low-grade.

Conclusions:

  • Combining erlotinib with MetMab is a promising strategy for advanced NSCLC patients with Met overexpression, significantly improving PFS and OS.
  • Met IHC is a crucial biomarker for patient selection, as the benefit is confined to Met-overexpressing tumors.
  • A phase III trial is underway to confirm these findings.

More Related Videos

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation15:04

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Published on: January 19, 2019

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma06:15

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

Published on: October 27, 2014

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...