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Novel Combinations Challenge Osimertinib Alone in EGFRm Lung Cancer

*January 2024*

While the standard-of-care recommendations can vary depending on the individual patient, EGFR tyrosine kinase inhibitors (TKIs) like osimertinib (Tagrisso) have played a pivotal role in the treatment of patients with EGFR-mutated lung cancer in recent years.

Osimertinib tends to be the preferred first-line treatment for most patients who harbor common EGFR mutations, including exon 19 deletions or L858R. When evaluated in the FLAURA study (NCT02296125), osimertinib led to superior efficacy and longer progression-free survival (PFS) rates when directly compared with older EGFR TKIs like gefitinib (Iressa) or erlotinib (Tarceva).

However, several drug combinations have shown promise in this space and can potentially improve patient outcomes compared with osimertinib alone. These studies include the phase 3 FLAURA2 trial (NCT04035486) of osimertinib with chemotherapy, the phase 3 MARIPOSA study (NCT04487080) of amivantamab-vmjw (Rybrevant) in combination with lazertinib (Leclaza), the phase 2 RAMOS trial (NCT03909334) of osimertinib and ramucirumab (Cyramza), and the phase 3 PAPILLON trial (NCT04538664) of amivantamab plus chemotherapy.

“The space has rapidly evolved in how we are treating patients, both for the common mutations like exon 19 deletion and L858R, which comprise the majority of EGFR mutations, but also some of the less common mutations such as exon 20 insertions,” Jonathan W. Riess, MD, told Targeted OncologyTM, in an interview.

In the interview, Riess, medical director of thoracic oncology, University of California, Davis Comprehensive Cancer Center, discussed the ever-changing EGFR-mutated lung cancer treatment landscape, highlighting a number of agents that are currently under development. Read more.