This study provides critical insights for the clinical combination of PEM → OSI regimens: (1) the 48 h interval sequential PEM → OSI strategy demonstrated optimal synergy in both PEM-sensitive and moderate-sensitive patients (Figure 2D,F,H and Tables S5, S7 and S9); (2) synergy appeared OSI-response dependent, with NSCLC cell lines exhibiting high EGFR/Bim expression likely benefiting maximally from this regimens; and (3) to avoid interfering with the next PEM cycle, brief interruption of OSI administration may be necessary during sequential PEM → OSI therapy across multiple cycles. Here, EGFR is linked to non-small cell lung carcinoma.