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If a lung cancer has a targetable mutation, give the pill first; immunotherapy works poorly in these tumours and raises the risk of severe side effects when a pill follows.
This sequence rule says that in non-small-cell lung cancer with a targetable driver such as EGFR, ALK, ROS1 or RET, a small-molecule kinase inhibitor comes first and immune checkpoint inhibitors later. Oncogene-addicted tumours have a low mutational burden and an immunosuppressive microenvironment, so PD-1 blockade works poorly, as the IMMUNOTARGET series showed, and the immune priming it leaves behind raises the risk of pneumonitis when osimertinib follows. Randomised first-line trials such as LIBRETTO-431, CROWN and MARIPOSA make targeted therapy with drugs such as osimertinib, lorlatinib and selpercatinib the standard. Chemotherapy, with or without an antibody-drug conjugate or immunotherapy, is held for later lines.
Shares CROWN, Lorlatinib, ALK, Osimertinib.
Shares Lorlatinib, RET, ALK, Osimertinib.
Shares CROWN, Lorlatinib, ALK, Non-small-cell lung cancer.
Shares LIBRETTO-431, Selpercatinib, Pembrolizumab.
Shares ROS1, Selpercatinib, RET, Non-small-cell lung cancer.
Shares ROS1, Selpercatinib, RET, Small-molecule kinase inhibitors.
Shares MARIPOSA, Osimertinib, EGFR, Non-small-cell lung cancer.