Combination therapy for treatment of cancer

1. A method of treating an estrogen-related cancer or tumor in a human comprising administering to the human in need thereof a therapeutically effective amount of a SERD in combination with a therapeutically effective amount of a CDK4/6 inhibitor, wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,

and wherein the CDK4/6 inhibitor is selected from:

or a pharmaceutically acceptable salt thereof; wherein the estrogen-related cancer or tumor is breast cancer, ovarian cancer, endometrial cancer, kidney cancer, uterine cancer, prostate cancer, or lung cancer.

2. The method of claim 1 , wherein the estrogen-related cancer is metastatic endocrine therapy resistant breast cancer.

3. The method of claim 1 , wherein the cancer is breast cancer.

4. The method of claim 3 , wherein the breast cancer is hormone receptor positive metastatic breast cancer.

5. The method of claim 3 , wherein the breast cancer is a tamoxifen resistant breast cancer.

6. The method of claim 3 , wherein the breast cancer is a triple negative breast cancer.

7. The method of claim 1 , wherein the human is further administered another chemotherapeutic agent in combination or alternation with the SERD and the CDK4/6 inhibitor.

8. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

12. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

14. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof,

and the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

18. The method of claim 17 , wherein the estrogen-related cancer is metastatic endocrine therapy resistant breast cancer.

19. The method of claim 17 , wherein the cancer is breast cancer.

20. The method of claim 19 , wherein the breast cancer is hormone receptor positive metastatic breast cancer.

21. The method of claim 19 , wherein the breast cancer is a tamoxifen resistant breast cancer.

22. The method of claim 17 , wherein the human is further administered another chemotherapeutic agent in combination or alternation with the SERD and the CDK4/6 inhibitor.

23. A pharmaceutical composition comprising a SERD, a CDK4/6 inhibitor, and a pharmaceutically acceptable carrier, wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,

and wherein the CDK4/6 inhibitor is selected from:

or a pharmaceutically acceptable salt thereof.

24. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

25. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

26. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

27. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

28. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

29. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

30. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising:

(i) a compound of structure:

or a pharmaceutically acceptable salt thereof;

(ii) a compound of structure:

or a pharmaceutically acceptable salt thereof; and

(iii) a pharmaceutically acceptable carrier.

32. A combination comprising a therapeutically effective amount of a SERD and a CDK4/6 inhibitor;

wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,

and wherein the CDK4/6 inhibitor is selected from:

or a pharmaceutically acceptable salt thereof.