Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib

Annals of Oncology : Official Journal of the European Society for Medical Oncology
A J SchoenfeldM D Hellmann

Abstract

Concurrent programmed death-ligand-1 (PD-(L)1) plus osimertinib is associated with severe immune related adverse events (irAE) in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity. We identified patients with EGFR-mutant NSCLC who were treated with PD-(L)1 blockade and EGFR- tyrosine kinase inhibitors (TKIs), irrespective of drug or sequence of administration (total n=126). Patient records were reviewed to identify severe (NCI-CTCAE v5.0 grades 3-4) toxicity. Fifteen percent [6 of 41, 95% confidence interval (CI) 7% to 29%] of all patients treated with sequential PD-(L)1 blockade followed later by osimertinib developed a severe irAE. Severe irAEs were most common among those who began osimertinib within 3months of prior PD-(L)1 blockade (5 of 21, 24%, 95% CI 10% to 45%), as compared with >3-12months (1 of 8, 13%, 95% CI 0% to 50%), >12months (0 of 12, 0%, 95% CI 0% to 28%). By contrast, no severe irAEs were identified among patients treated with osimertinib followed by PD-(L)1 (0 of 29, 95% CI...Continue Reading

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Jun 20, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew J Piper-VallilloZofia Piotrowska
May 18, 2019·Archives of Pathology & Laboratory Medicine·Eric H Bernicker
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