The paired baseline and progression sample analysis identified the emergence of acquired mutations, EGFR C797S (n = 1), KRAS G12D (n = 1), and PIK3CA E545K mutations (n = 2), in the progression samples. One of these progression tissue samples with an acquired PIK3CA mutation also lost EGFR....Our multi-layered molecular analysis of osimertinib-resistant patients’ clinical samples and patient-derived cancer models demonstrates a diverse spectrum of osimertinib resistance...

In this subset of patients, PIK3CA mutations were the alterations most frequently detected upon disease progression, being found in four patients. Specifically, we identified the p.E545K mutation in one patient (Table 2)....Table 2 Molecular alterations detected in ctDNA upon progression to osimertinib treatment.