Dr Forde on Perioperative Osimertinib and Biomarker Testing in Resectable EGFR-Mutated NSCLC

“[It is] recommended that every patient with clinical stage II or III lung cancer should have biomarker testing prior to surgery. Now, that’s not always easy, but I would, if possible, prioritize it so they get the best systemic therapy.”

Patrick Forde, MBBCh, PhD, the Patrick Prendergast Professor of Clinical Immuno-Oncology at the Trinity St James’s Cancer Institute, Trinity College Dublin, a consultant medical oncologist at St James’s Hospital in Dublin, and a professor at Johns Hopkins University, discussed where neoadjuvant and adjuvant osimertinib (Tagrisso) fit in the management of resectable EGFR-mutated non–small cell lung cancer (NSCLC), and how perioperative immunotherapy should be approached in patients with EGFR or ALK alterations at the 44th Annual PER® Chemotherapy Foundation Symposium.

Long-term follow-up from the phase 3 ADAURA trial (NCT02511106) of patients with resected stage IB to IIIA disease continues to show a survival benefit with 3 years of adjuvant osimertinib, Forde said. Additionally, the phase 3 NeoADAURA trial (NCT04351555), showed benefit with neoadjuvant osimertinib with or without chemotherapy, he noted.

Forde said he prioritizes neoadjuvant therapy for clinical stage IIIA or IIIB tumors, where the goal is downstaging since the risk of micrometastatic disease is high and to start the TKI as early as possible. Patients with stage II disease can proceed to upfront surgery followed by adjuvant osimertinib, he said.

Patients with EGFR or ALK alterations do not derive meaningful benefit from PD-1/PD-L1 blockade in advanced disease, Forde noted. Early-stage data are more limited, but small subgroups in perioperative trials have not shown a clear benefit either, he said. He added that immunotherapy given before an EGFR TKI may also enhance TKI toxicity.

Patients with a targetable alteration should generally proceed to surgery, with neoadjuvant therapy for a few, followed by adjuvant TKI, Forde concluded. Those without an actionable alteration may receive chemoimmunotherapy, surgery, and potentially adjuvant immunotherapy, he said.