阅读说明：本技术 Cdk4/6抑制剂与egfr抑制剂联合在制备***疾病的药物中的用途 (Use of CDK4/6 inhibitor in combination with EGFR inhibitor for the manufacture of a medicament for the treatment of neoplastic diseases ) 是由 张蕾 杨昌永 廖成 张连山 于 2019-05-22 设计创作，主要内容包括：本发明提供了CDK4/6抑制剂与EGFR抑制剂联合在制备治疗肿瘤疾病的药物中的用途。具体而言,本发明提供一种细胞周期蛋白依赖性激酶4和6抑制剂(CDK4/6i)与人表皮生长因子受体抑制剂(EGFRi)联合在制备预防或治疗肿瘤疾病的药物中的用途。(The invention provides the use of a CDK4/6 inhibitor in combination with an EGFR inhibitor for the manufacture of a medicament for the treatment of a neoplastic disease. In particular, the invention provides the use of a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) in combination with a human Epidermal Growth Factor Receptor Inhibitor (EGFRI) for the preparation of a medicament for the prevention or treatment of a neoplastic disease.)

Use of a CDK4/6 inhibitor in combination with an EGFR inhibitor for the preparation of a medicament for the prevention or treatment of a neoplastic disease.

Use according to claim 1, characterized in that: the neoplastic disease is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, melanoma, brain tumor, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, skin cancer, glioblastoma, neuroblastoma, sarcoma, liposarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck tumor, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, bile duct cancer, or chorioepithelial cancer, preferably non-small cell lung cancer.

Use according to claim 1, characterized in that: the tumor disease is EGFR mutation tumor disease.

Use according to claim 3, characterized in that: the EGFR mutant tumor disease is non-small cell lung cancer, and the preferred EGFR mutant is selected from L858R EGFR mutant and/or T790M EGFR mutant.

Use according to claim 2, characterized in that: the non-small cell lung cancer is selected from squamous cell carcinoma and non-squamous cell carcinoma, preferably non-squamous cell carcinoma.

Use according to any one of claims 1 to 5, characterized in that: the CDK4/6 inhibitor is selected from abemaciclib, ribociclib, palbociclib, alvocidib, trilaciclib, voriciclib, AT-7519, G1T-38, FLX-925, INOC-005, G1T28-1, BPI-1178, gossypin, G1T30-1, GZ-38-1, P-276-00, staurosporine, R-547, PAN-1215, PD-0183812, AG-024322, NSC-625987, CGP-82996, PD-171851 or a compound shown in formula (I) or a pharmaceutically acceptable salt thereof, preferably abemaciclib, ribociclib, palbociclib, alvocidib or a compound shown in formula (I) or a pharmaceutically acceptable salt thereof, most preferably a compound shown in formula (I) or a pharmaceutically acceptable salt thereof,

use according to any one of claims 1 to 5, characterized in that: the EGFR inhibitor is selected from osimertinib, gefitinib, erlotinib, olmutinib, icotinib, pyrotinib, vandetanib, brigitinib, dacomitinib, afatinib, neratinib, lapatinib, ABT-414, varlitinib, HLX-07, tesetinib, thelitatinib, epitinib succinate, S-222611, pozitinib, AST-2818, GNS-1480, maertinib, AP-32788, AZD-3759, nazurttinib, Sym-013, allitinib tosilate, tauxotinib bride, QL-SCTP-101, JNJ-61186372, SKLB-SKIRIB, S-1028, xylinity-020, xylidine-1118, dolicib-94, BCB-200, BCB-H-200, BCB-H-200, BCB-H-200, BCB-H-200, BCB-P-H, preferably olmutinib, afatinib, osimertinib, CK-101, erlotinib, icotinib, gefitinib or a compound of formula (II) or a stereoisomer, complex or pharmaceutically acceptable salt thereof, most preferably a compound of formula (II) or a stereoisomer, complex or pharmaceutically acceptable salt thereof,

use according to claim 6, characterized in that: the pharmaceutically acceptable salt of the compound shown in the formula (I) is isethionate.

Use according to claim 7, characterized in that: the pharmaceutically acceptable salt of the compound shown in the formula (II) is mesylate.

Use according to any one of claims 1 to 9, characterized in that: the CDK4/6 inhibitor is administered in a dose selected from 1-1000mg once a day, twice a day, three times a day; the dose range of the EGFR inhibitor is selected from 1-1000mg, and the dosage is once a day, twice a day and three times a day.

Use according to claim 10, characterized in that: the weight ratio of the CDK4/6 inhibitor to the EGFR inhibitor is selected from 0.001:1 to 1000:1, preferably 0.01:1 to 100:1, most preferably 0.05:1 to 50: 1.

Use according to claim 10, characterized in that: said CDK4/6 inhibitor is administered once daily at a dose selected from the group consisting of 25mg, 50mg, 75mg, 100mg, 125mg, 150mg, 175 mg; the EGFR inhibitor is administered once daily at a dose selected from 55mg, 110mg, 220mg, 260 mg.

A pharmaceutical composition comprising an inhibitor of CDK4/6 according to any one of claims 1-12 and an EGFR inhibitor, together with one or more pharmaceutically acceptable carriers, excipients, diluents.

A pharmaceutical kit comprising the pharmaceutical composition of claim 13.