Standard Treatment May Not Be Best for Exon 20-Mutant Lung Cancer

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Rybrevant outperformed other therapies for patients with exon 20 insertion-mutant, advanced non-small cell lung cancer in a clinical trial, highlighting the importance of personalized medicine.

Rybrevant (amivantamab-vmjw) outperformed other therapies for the treatment of patients with exon 20 insertion-mutant, advanced non-small cell lung cancer (NSCLC), according to recent research presented at the 2023 European Lung Cancer Congress in Denmark.

“Real-world analyses help advance understanding of medicines like Rybrevant and may inform treatment selection in patients with NSCLC and EGFR exon 20 insertion mutations,” study author Dr. Nicolas Girard, professor of respiratory medicine at Versailles Saint Quentin University and head of Curie-Montsouris Thorax Institute in Paris, said in an interview with CURE®.

“This study sheds light on the need for evidence-based treatment decisions in the real-world management of patients with this disease and shows the potential use of targeted therapies in patients with gene-mutated NSCLC.”

READ MORE: Rybrevant Is Efficacious, Tolerable in EGFR Exon 20-Mutant Lung Cancer

Can you explain the basis for your study and why it was important to conduct?

The analysis evaluated the relative effectiveness of Rybrevant in the phase 1 CHRYSALIS trial compared with real-world datasets in the U.S. and (European Union) of other commonly used anti-cancer therapies that are not approved specifically for patients with exon 20 insertion mutations such as EGFR tyrosine kinase inhibitors (TKIs) (69 patients), immunotherapy (91 patients), non-platinum chemotherapy (87 patients), vascular endothelial growth factor inhibitor (VEGFi) plus chemotherapy (57 patients) and other real-world therapies (79 patients) after adjusting for differences in patient characteristics. Key endpoints were overall survival (time during and after treatment until death of any cause), progression-free survival (time from treatment until disease worsens), time to next treatment and overall response rate (percentage of patients whose cancer shrinks or disappears from treatment).

Exon 20 insertions are uncommon, accounting for 4-12% of all EGFR mutations, and is a different disease from common EGFR including EGFR exon 19 deletions or L858R mutations. In clinical practice, patients with exon 20 insertions may be treated in the same way as patients that have other activating EGFR mutations, resulting in treatment with limited benefit.

Before the use of Rybrevant, what were outcomes like for patients with exon 20 insertion mutant NSCLC? Why was this therapy needed?

Rybrevant bested real-world treatments in overall survival.

Rybrevant bested real-world treatments in overall survival.

Patients with EGFR exon 20 insertion mutations have poorer outcomes with a median overall survival of 16.2 months and a real-world five-year overall survival of 8% in the frontline setting, which is worse than patients with EGFR exon 19 deletions or L858R mutations, who have a median overall survival of 25.5 months and a real-world five-year overall survival of 19%.

The standard of care for common EGFR mutations, such as EGFR TKIs, are generally inactive against exon 20 insertion mutations and are not FDA approved for these patients.

Rybrevant was the first targeted therapy approved for the treatment of patients with NSCLC with EGFR exon 20 insertions who progressed on platinum chemotherapy. After a median follow-up of 19.2 months, the median overall survival with Rybrevant treatment was 23 months compared to 16 months in the real world.

In the conclusion of the study, you mentioned that education on the appropriate treatment is important to advance quality of care. Can you elaborate on this?

The study has shown that the standard of care for common EGFR mutations, such as EGFR TKIs, and other therapies may not be as effective in exon 20 mutations and are not FDA approved for these patients. Education is critical to help understand the difference between exon 20 and common EGFR and the appropriate choice of therapies.

What conversations should patients have with their providers before starting Rybrevant?

Patients should speak with their doctors to learn about genetic testing and what personalized treatment option is best for them. Precision medicine offers the opportunity for more effective treatment targeted against the biological mechanisms causing disease. Such an approach has the potential to optimize treatment outcomes for patients and improve quality of care.

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