<b>Conclusion:</b> In these two case reports, saliva-based EFIRM platform demonstrates a high level of concordance to plasma-based platforms (ddPCR and NGS) for longitudinally monitoring the combination of <i>EGFR</i> and <i>PIK3CA</i> ctDNA and can be a useful platform to monitor tumor progression and response to targeted therapy in NSCLC patients. The gene discussed is PIK3CA; the disease is neoplasm.