Of the remaining 28 patients who did not have an identified EGFR-based and/or MET-based osimertinib resistance mechanism, 18 had unknown mechanisms (of these, one had neither tissue nor ctDNA and 13 had ctDNA testing but no tumor testing), and 10 had EGFR-independent and/or MET-independent resistance mechanisms, such as alterations in PIK3CA, KRAS and PTEN, and mutations in cell cycle genes, identified by NGS (Fig. 2d and Supplementary Table 7). The gene discussed is PIK3CA; the disease is neoplasm.