Combination therapy involving diaryl macrocyclic compounds
The present disclosure relates to methods and compositions for treating cancer with a diaryl macrocycle in combination with at least one other cancer therapeutic, such as an EGFR inhibitor.
1. A method for treating cancer in a patient in need thereof, the method comprising the step of administering to the patient a therapeutically effective amount of a compound having structure:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an EGFR inhibitor selected from afatinib, dacomitinib, gefitinib, and osimertinib, or a pharmaceutically acceptable salt thereof,
wherein the cancer is lung cancer.
2. The method of claim 1 , wherein the lung cancer is non-small cell lung cancer (NSCLC), adenocarcinoma, lung squamous cell carcinoma, large cell carcinoma, large cell neuroendocrine tumor, or small cell lung cancer (SCLC).
3. The method of claim 1 , wherein the lung cancer is non-small cell lung cancer or metastatic non-small cell lung cancer.
4. The method of claim 1 , wherein the EGFR inhibitor is afatinib or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the EGFR inhibitor is dacomitinib or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the EGFR inhibitor is gefitinib, or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the EGFR inhibitor is osimertinib or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , comprising oral administration.
9. The method of claim 1 , comprising from 0.1 mg to 1 g daily of the compound, or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , comprising from 50 mg to 250 mg daily of the compound, or a pharmaceutically acceptable salt thereof.
11. The method of claim 1 , comprising from 50 mg to 250 mg daily of the EGFR inhibitor, or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 , wherein the compound and the EGFR inhibitor are individually formulated, and administered at the same time.
13. The method of claim 1 , comprising sequential administration of the compound and the EGFR inhibitor.
14. The method of claim 13 , comprising administering the compound first, and administering the EGFR inhibitor second.
15. The method of claim 13 , comprising administering the EGFR inhibitor first, and administering the compound second.