Dr Schneider on Treatment Considerations After Osimertinib in EGFR+ NSCLC

Jaime Schneider, MD, PhD, medical oncologist, assistant in medicine, Center for Thoracic Cancers, Massachusetts General Hospital, instructor of medicine, Harvard Medical School, discusses treatment considerations for patients with EGFR-mutant non–small cell lung cancer (NSCLC) that progresses on osimertinib (Tagrisso).

Primarily, attention within the treatment of EGFR-mutant NSCLC after progression on osimertinib is given to identifying on-target resistance alterations, such as EGFR C797S mutations, which are frequently encountered in this patient population, Schneider begins. Detection of such alterations prompts consideration for enrollment in clinical trials investigating fourth-generation EGFR TKIs capable of addressing these mutations, Schneider explains.

Moreover, Schneider mentions that off-target resistance mechanisms, such as MET amplification, are noted as drivers of acquired resistance in patients whose disease relapses on osimertinib. Treatment strategies involve utilizing TKIs targeting MET, alongside emerging data indicating efficacy of antibody-drug conjugates (ADCs) directed against MET activity.

Schneider highlights that there is the potential for lineage transformation upon osimertinib resistance. Consequently, routine tissue biopsy is important to detect any histological changes, facilitating tailored therapeutic decisions.

Clinical practice often involves continuing osimertinib to prevent rebound phenomena, Schneider explains. However, the decision to maintain osimertinib alongside chemotherapy varies depending on the chemotherapy regimen employed.

Schneider notes that while osimertinib may be continued with carboplatin plus pemetrexed regimens; however, the agent should not be continued when incorporating immunotherapy agents in combination with chemotherapy regimens, necessitating careful evaluation of treatment modalities.

Management strategies for patients progressing on osimertinib entail meticulous assessment of resistance alterations, consideration of clinical trial enrollment for novel agents targeting specific mutations, and vigilance for potential lineage transformations. The approach to continuing osimertinib alongside chemotherapy necessitates individualized consideration of treatment regimens, weighing the potential benefits and risks associated with each approach.