Options for Patients with NSCLC That Has Progressed After Osimertinib
Osimertinib (Tagrisso) has a strong foothold as first-line therapy for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC), but resistance to the third-generation EGFR tyrosine kinase inhibitor is a major stumbling block.
“Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second-line therapy for patients whose disease progresses during front-line osimertinib,” advised Zofia Piotrowska, MD, of Massachusetts General Hospital in Boston, and colleagues.
In a review article, Piotrowska’s group offered an “evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression,” including the following key points:
Slow, asymptomatic progression often does not require an immediate change in treatment, and many patients can safely continue osimertinib beyond initial radiographic progression
Add-on locally ablative therapy to osimertinib is an option for patients with oligoprogression
MET alterations, EGFR C797X, small-cell lung cancer transformation, and oncogene fusions are the most common mechanisms of osimertinib resistance
“For patients with an EGFR mutation whose disease progresses on osimertinib and who move to second-line chemotherapy, the role of combination chemoimmunotherapy is not well understood,” and, as a result it is possible that “both a PD-L1 inhibitor and antiangiogenesis agent are required to improve on chemotherapy for patients with EGFR-positive disease”
Metastasis to the central nervous system (CNS) is common in these patients (about 20% of the FLAURA trial population had CNS metastases at presentation), and “osimertinib’s strong CNS penetration has likely contributed to the drug’s success”