RET-TKI + EGFR-TKI

Combination therapy of a **RET tyrosine kinase inhibitor (RET-TKI)** and an **epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)**, most commonly exemplified by pairing drugs such as **selpercatinib** (RET-TKI) or **pralsetinib** (RET-TKI) with **osimertinib** (EGFR-TKI). This approach is used for patients with **non-small cell lung cancer (NSCLC)** harboring EGFR mutations who develop acquired **RET fusions** as a secondary resistance mechanism after EGFR-TKI treatment. The combination inhibits both the EGFR and RET pathways, aiming to overcome acquired resistance and suppress tumor growth. The combination has been evaluated in clinical and compassionate use settings, showing clinical benefit and an acceptable safety profile, although resistance mechanisms and potential toxicities require close monitoring[1][2][5].