CN116829152A - Application of Icotinib in postoperative adjuvant therapy of non-small cell lung cancer - Google Patents

Application of Icotinib in postoperative adjuvant therapy of non-small cell lung cancer Download PDF

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CN116829152A
CN116829152A CN202280011300.2A CN202280011300A CN116829152A CN 116829152 A CN116829152 A CN 116829152A CN 202280011300 A CN202280011300 A CN 202280011300A CN 116829152 A CN116829152 A CN 116829152A
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icotinib
pharmaceutically acceptable
acceptable salt
lung cancer
use according
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周彩存
谭芬来
何建行
苏春霞
梁文华
汪洋
袁晓玢
杨敏
刘勇
何伟
何祥波
刘国峰
郝志栋
张丹丹
季东
毛力
丁列明
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Betta Pharmaceuticals Co Ltd
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract

Application of Icotinib in postoperative adjuvant treatment of non-small cell lung cancer is provided. The treatment effect of the Excritinib for the NSCLC patient with EGFR gene sensitive mutation after operation is obviously superior to that of standard auxiliary chemotherapy, and the safety is better than that of the standard auxiliary chemotherapy, namely, the Excritinib auxiliary treatment can provide safe and effective treatment selection for the NSCLC patient in the II-IIIA phase.

Description

Application of Icotinib in postoperative adjuvant therapy of non-small cell lung cancer Technical Field
The invention belongs to the technical field of medicines, and relates to application of icotinib in postoperative adjuvant therapy of non-small cell lung cancer.
Background
Lung cancer is one of the leading causes of death in cancer patients in our country and even worldwide, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancer patients. According to the disease stage, the survival rate of patients after NSCLC operation is 25-73% in 5 years. Surgical excision is one of the main treatment means of patients with early NSCLC, so that clinical cure of lung cancer is possible. However, even with surgical treatment, 40-75% of stage i-IIIA NSCLC patients relapse and therefore die within 5 years. Therefore, the guidelines of each country recommend postoperative adjuvant treatment for patients in stage II-IIIA who have had their lesions completely resected. National Comprehensive Cancer Network (NCCN) in 2013, recommended post-operative adjuvant chemotherapy for post-operative NSCLC patients with complete resection in stage IB-IIIA, and chemotherapy regimens that may be used include combination of vinorelbine, etoposide, vinblastine, gemcitabine, docetaxel, or pemetrexed on a cisplatin basis; for patients with concomitant diseases and intolerance to cisplatin treatment, a combination regimen of carboplatin and paclitaxel may be used for chemotherapy. The national primary lung cancer diagnosis and treatment standard (2011) recommends that the completely resected phase II-III patients receive the platinum-containing two-drug scheme postoperative adjuvant chemotherapy. Although post-operative adjuvant chemotherapy brings clinical and survival benefits to patients over placebo, the adjuvant chemotherapy DFS is approximately between 19-28 months and has severe hematological toxicity. There is a great clinical need for a highly effective and low toxicity therapeutic regimen for surgically resectable patients.
Small molecule tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) have shown excellent efficacy in advanced NSCLC, with gefitinib, erlotinib and icotinib being representative drugs. Whether or not such drugs can bring benefit to patients in stage II-IIIA becomes a focus of attention in the clinical field, and at present, a plurality of random control clinical studies have been tried and explored. The EVAN study is a randomized, controlled, phase II study comparing erlotinib and chemotherapy (vinorelbine/cisplatin regimen) for post-operative adjuvant treatment of stage IIIA EGFR mutant NSCLC patients, 102 cases of patients following EGFR sensitive mutation NSCLC in stage IIIA after R0 excision in the co-group, the main efficacy index is disease-free survival (DFS), and the results show that erlotinib group and chemotherapy group DFS are 42.4 months vs 21.0 months, P < 0.0001, respectively. One randomized, control, phase III ADJUVANT study (CTONG 1104) was performed on 222 completely resected NSCLC patients with phase II-IIIA EGFR mutations, who received gefitinib (2 years of continuous dosing) and chemotherapy (4-6 cycles) at random, with DFS for 30.8 months and 19.8 months, respectively, hr=0.56, p=0.001, and gefitinib ADJUVANT treatment was significantly better than the chemotherapy group. Preliminary exploration of the same type of drug in the II-IIIA phase proves the curative effect of gefitinib and erlotinib in the II-IIIA phase NSCLC patients as postoperative adjuvant treatment compared with standard treatment (chemotherapy), but the two researches are not registered researches aiming at applying to the market, and have certain limitations in terms of data robustness degree and target crowd selection. In the ADJUNANT study, the DFS of gefitinib group only takes place for 30.8 months, i.e. patients relapse half a year after the end of the drug; whereas the EVAN study is a two-phase study with a small sample size, relatively inadequate data, and the study was only performed on group IIIA patients, for which neither drug was approved.
Although other postoperative adjuvant treatment regimens exist in the prior art, for example, EGFR mutant positive non-small cell lung cancer patients receive a standard adjuvant chemotherapy regimen (vinorelbine+cisplatin/pemetrexed+cisplatin) for 4 cycles, further studies on clinical treatment of more postoperative adjuvant treatment non-small cell lung cancer patients are still needed, providing a new medication option for medical workers and patients.
Disclosure of Invention
In view of this, it is an object of the present invention to provide a use of icotinib or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and/or co-treatment of a patient with a tumor, preferably non-small cell lung cancer, further EGFR mutation positive non-small cell lung cancer, wherein the patient has been surgically completely resected from the lesion prior to administration of icotinib or a pharmaceutically acceptable salt thereof.
As a specific embodiment of the foregoing use, the non-small cell lung cancer is stage II-IIIA non-small cell lung cancer.
As a specific embodiment of the foregoing use, the EGFR mutation is an EGFR19 exon deletion or a 21 exon L858R mutation.
As a specific embodiment of the foregoing use, the EGFR mutation is not the 20 exon T790M mutation.
As a specific embodiment of the foregoing use, the patient does not have tumor recurrence or/and metastasis prior to administration of the icotinib or a pharmaceutically acceptable salt thereof.
As a specific embodiment of the foregoing use, the patient has not received systemic anti-tumor therapy, including chemotherapy, radiation therapy or targeted therapy, prior to administration of the icotinib or a pharmaceutically acceptable salt thereof; further, the targeted therapies include, but are not limited to, monoclonal antibodies, small molecule tyrosine kinase inhibitors, and the like.
As a specific embodiment of the foregoing use, the medicament comprises icotinib or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
As a specific embodiment of the foregoing use, the pharmaceutically acceptable salt of icotinib is icotinib hydrochloride.
As a specific embodiment of the foregoing use, the icotinib or a pharmaceutically acceptable salt thereof is administered three times daily. In another embodiment, the icotinib hydrochloride is administered three times daily.
As a specific embodiment of the aforementioned use, the drug is administered in a single dose of 125mg of Icotinib.
As a specific embodiment of the aforementioned use, the medicament is administered orally.
As a specific embodiment of the aforementioned use, the medicament is a tablet.
It is another object of the present invention to provide a method for the treatment and/or adjuvant treatment of EGFR-mutation positive non-small cell lung cancer in a tumor patient, comprising administering to the patient, ecritinib or a pharmaceutically acceptable salt thereof, wherein the patient has been surgically completely resected from the lesion prior to administration of Ecritinib or a pharmaceutically acceptable salt thereof.
Definition and description
Stage II-IIIA non-small cell lung cancer: classification was according to united states joint committee for cancer [ AJCC, american Joint Committee on Cancer ] lung cancer TNM stage seventh edition.
EGFR mutant positive NSCLC and diagnostic method
In 2004, activating mutations in exons 18-21 of EGFR were reported to be associated with responses to EGFR-TKI therapy in NSCLC (Science [ Science ] [2004], volume 304, 1497-1500;New England Journal ofMedicine [ New England journal of medicine ] [2004], volume 350, 2129-2139). It is estimated that these mutations are prevalent in about 10% -16% of NSCLC patients in the united states and europe, and about 30% -50% of NSCLC patients in asia. Among the two most significant EGFR activating mutations are the deletion of exon 19 and the missense mutation in exon 21. Exon 19 deletions account for approximately 45% of known EGFR mutations. Eleven different mutations resulting in three to seven amino acid deletions were detected in exon 19, and all of these mutations were centered on the consistently deleted codons of amino acids 747-749. The most significant deletion of exon 19 is E746-A750. The missense mutation in exon 21 accounts for about 39% -45% of known EGFR mutations, with the substitution mutation L858R accounting for about 39% of the total mutations in exon 21 (j. Thorac. Oncol. [ journal of chest oncology ] [2010], 1551-1558). The skilled artisan will recognize mutations in EGFR that are associated with improved response to EGFR-TKI therapy.
The skilled artisan will recognize that there are many methods for detecting EGFR activating mutations. These methods include tumor tissue-based diagnostic methods and plasma-based diagnostic methods. Typically, EGFR mutation status is first assessed using a tumor tissue biopsy sample derived from the patient. If a tumor sample is not available, or if the tumor sample is negative, a plasma sample can be used to assess EGFR mutation status. A specific example of a suitable diagnostic method for detecting EGFR activating mutations, in particular for detecting exon 19 deletions or L858R substitution mutations, is the human EGFR gene mutation detection kit (fluorescent PCR method, xiaomen Aide Biotechnology Co., ltd.).
Definition of complete excision surgery (refer to the "diagnosis and treatment Specification for Primary Lung cancer" 2015 edition made by national institutes of health and family planning): complete resection (R0 surgery) in addition to complete resection of the primary lesion, systemic phylum and mediastinal lymph node (N1 and N2 lymph node) resections should be routinely performed and indicated for pathological examination. A minimum of 3 mediastinal drainage areas (N2 stations) including the subcarina lymph nodes were swept or sampled to ensure as much as possible a total resection of the lymph nodes. The recommended right thoracic lymph node clearance range is: the range of lymph node clearance for group 2R, 3a, 3p, 4R, 7-9 and surrounding soft tissue, left thoracic lymph node: 4L, 5-9 groups of lymph nodes and surrounding soft tissue. Incomplete resection (R1) procedure is defined when there is an extranodal violation of the resected mediastinum or marginal lymph nodes of the pulmonary lymph nodes; when lymph nodes have been confirmed to metastasize but cannot be resected, then a palliative resection (R2) procedure is defined; an indeterminate surgical resection is defined when there are still cancerous cells under the lymph node microscope of the highest resection group, or when lymph node clearing does not meet the above requirements.
Ecritinib and pharmaceutical composition thereof
The icotinib has the following chemical structure:
the chemical name of the free base of icotinib is known as 4- [ (3-ethynylphenyl) amino ] -6, 7-benzo-12-crown-4-quinazoline.
The icotinib can exist in the form of the following hydrochloride salt: 4- [ (3-ethynylphenyl) amino group]-6, 7-benzo-12-crown-4-quinazoline hydrochloride. Icotinib hydrochloride is also known as
Examples
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. In the examples below, unless otherwise indicated, the test methods described are generally carried out under conventional conditions or conditions recommended by the manufacturer; the raw materials and the reagents can be obtained in a commercially available mode.
Multicenter, randomized, open, phase III clinical study of Excrinib contrast-based adjuvant chemotherapy for postoperative adjuvant treatment of EGFR-associated sensitive mutant non-small cell lung cancer in phase II-IIIA
The research method comprises the following steps:
the study was a randomized, multicentric, positive drug control phase III clinical study. Subjects following complete excision (R0) surgery of stage II-IIIA non-small cell lung cancer (NSCLC) who were planned to be positive for Epidermal Growth Factor Receptor (EGFR) sensitive mutation in group 320 centrally located across country, at 1:1 to the icotinib group or standard adjuvant chemotherapy group, the stratification factors including disease stage (stage II/IIIA), mutation site (19 del/21L 858R), lobed/total lung excision. Group 322 subjects were actually enrolled, with the Excotinib group 161 and the standard adjuvant chemotherapy group 161.
The Excritinib group subjects received the 125mg tablet of Excritinib hydrochloride three times daily, one at a time, orally for 24 months before the subjects developed tumor recurrence metastasis or developed intolerable toxic reactions. Standard adjuvant chemotherapy group subjects received a standard adjuvant chemotherapy regimen of 4 cycles of vinorelbine in combination with cisplatin or pemetrexed in combination with cisplatin (vinorelbine + cisplatin/pemetrexed + cisplatin), wherein squamous carcinoma subjects received vinorelbine in combination with cisplatin chemotherapy, and the choice of postoperative adjuvant chemotherapy regimen for non-squamous carcinoma subjects was determined by the investigator based on the physical condition and tolerability of the subject.
Study purposes:
main research purpose
Comparing disease-free survival (DFS) between the two groups
Secondary research purposes
Comparison of 3 year, 5 year DFS Rate between two groups
Total lifetime (OS), 5 years OS rate
Quality of life assessment (HRQOL)
Compare the safety and tolerability of the two groups
Prognosis risk model analysis
Diagnostic and primary inclusion criteria:
criteria for inclusion
Subject formulas meeting all of the following criteria can be entered into the selection study:
1. after complete surgical excision (according to the ' primary lung cancer diagnosis and treatment Specification ' 2015 edition ' made by the national health and family planning committee), the patient is pathologically confirmed to be a non-small cell lung cancer subject in stage II-IIIA;
2. the presence of EGFR19 exon deletion or 21 exon L858R mutation;
3. subjects who may be adjunctively treated 3-8 weeks after surgery;
4. the age is more than or equal to 18 years old and less than or equal to 70 years old;
5. physical condition ECOG scores 0-1;
6. the expected survival time is at least 1 year;
7. the level of organ function must meet the following requirements:
1) Bone marrow: absolute Neutrophil Count (ANC) greater than or equal to 2.0X10 9 The ratio of the total amount of the components to the total amount of the components is greater than or equal to 100 multiplied by 10 9 The haemoglobin is more than or equal to 9g/dl;
2) Liver: bilirubin is less than or equal to 1.5 times the upper limit of normal values, and aspartate Aminotransferase (AST) and alanine Aminotransferase (ALT) are less than or equal to 2.5 times the upper limit of normal values;
3) Kidney: serum creatinine is less than or equal to 1.25 times of the upper limit of normal value or creatinine clearance rate is more than or equal to 60ml/min;
8. women of childbearing age must undergo pregnancy tests within 7 days before beginning treatment and have negative results and take contraceptive measures within 3 months during and after the end of treatment; male of child bearing age: contraceptive measures are taken within 3 months after the surgical sterilization or treatment period is finished;
9. understand and voluntarily sign written informed consent.
Exclusion criteria
Subjects meeting any of the following criteria were not enrolled in the study:
1. other malignancies were diagnosed or treated within 5 years of the randomized group of the present study (subjects with resected basal cell carcinoma of the skin or other carcinoma in situ are not listed);
2. systemic anti-tumor treatments, including chemotherapy, radiation therapy, or targeted therapies (including but not limited to monoclonal antibodies, small molecule tyrosine kinase inhibitors, etc.), were used prior to the study group entry;
3. the lung cancer operation is a right lung total excision subject;
4. subjects with the 20 exon T790M mutation and other rare mutations, double mutations;
5. condition of each organ system of the subject:
1) Prior to suffering from interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis requiring hormonal treatment or any active interstitial lung disease with clinical evidence;
2) CT scan at baseline found the presence of interstitial lung disease;
3) Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease) exists at the discretion of the investigator;
4) Any unstable systemic disease (including active infection, hypertension III, unstable angina, congestive heart failure, liver and kidney or metabolic disease);
5) Subjects who are not receiving oral administration, need intravenous high-energy nutrition, have previously undergone surgery to affect absorption, or have active peptic ulcers;
6) Any obvious ocular abnormalities, particularly severe dry eye syndrome, keratoconjunctivitis sicca, severe exposed keratitis, or other diseases that may increase epithelial damage;
7) Past history of well-defined neurological or psychiatric disorders including epilepsy or dementia.
6. Functional level of lesions of each organ of a subject
1) Bone marrow: absolute Neutrophil Count (ANC)<2.0×10 9 /L(2，000/mm 3 ) Platelets<100×10 9 L or hemoglobin<9g/dl；
2) Liver: serum bilirubin > upper limit of normal value 1.5 times;
3) Serum creatinine > 1.25 times of normal standard value;
4) Any evidence of other diseases, neurological or metabolic disorders, physical examination or laboratory examination results reasonably suspects the possibility of a disease or the presence of an anti-indication using the relevant drug or putting the subject at high risk of treatment-related complications.
7. A subject allergic to vinorelbine/pemetrexed/cisplatin or icotinib;
8. pregnant or lactating women;
9. researchers believe that the subject is not necessarily able to complete the study or is not necessarily able to comply with the requirements of the study (for regulatory or other reasons);
10. the subject had tumor lesions.
The usage amount is as follows:
icotinib group:
125 mg/tablet of Excritinib, one at a time, three times a day, orally, 24 months in succession or recurrent metastasis of tumors or intolerable toxic reactions.
Standard adjuvant chemotherapy group:
standard adjuvant chemotherapy group subjects received a standard adjuvant chemotherapy regimen of 4-cycle vinorelbine in combination with cisplatin or pemetrexed in combination with cisplatin. Wherein the squamous carcinoma subjects receive vinorelbine in combination with cisplatin chemotherapy, and the choice of a non-squamous carcinoma subject postoperative adjuvant chemotherapy regimen is determined by the researcher based on the physical condition and tolerability of the subject.
Vinorelbine + cisplatin: vinorelbine 25mg/m 2 Intravenous administration (intravenous bolus or intravenous drip), day 1 and day 8; cisplatin 75mg/m 2 Intravenous drip, day 1 or total 3 divided administration; day 21 is a period of 4 consecutive periods, or until the tumor relapses to metastasize or an intolerable toxic response occurs.
Pemetrexed + cisplatin (for non-squamous cancer subjects only): pemetrexed 500mg/m 2 Intravenous drip, day 1; cisplatin 75mg/m 2 Intravenous drip, day 1 or total 3 divided administration; day 21 is a period of 4 consecutive periods, or until the tumor relapses to metastasize or an intolerable toxic response occurs.
If the subject is not receiving chemotherapy due to toxicity, the administration may be delayed by no more than 14 days, and once delayed by more than 14 days, the subject will terminate the treatment; however, even if a subject experiences a delay in treatment, tumor assessment should still be performed as planned.
Evaluation index:
effectiveness index:
1) Main therapeutic effect index
·DFS
2) Secondary efficacy index
DFS rate of 3 years, 5 years
OS Rate 5 years
·OS
Safety index:
adverse Event (AE)
Serious Adverse Events (SAE)
Vital signs and physical examination
Laboratory examination
Electrocardiogram (ECG)
Quality of life assessment (HRQOL)
The statistical method comprises the following steps:
statistical description is carried out on metering data by adopting mean, standard deviation, median, quartile (Q1, Q3), maximum value, minimum value and the like; the classification data or the grade data is described by indexes such as frequency, percentage and the like. All hypothesis testing significance levels (alpha) were bilateral 0.05, unless otherwise specified.
Staging analysis
The interim analysis is scheduled to occur when the endpoint event number reaches 50% (98/196) of the final analysis event number, and the alpha consumption function uses the Lan-Demets alpha consumption function of the O' Brien-Fleming boundary. Nominal alpha at the interim analysis was 0.003 and nominal alpha at the final analysis was 0.049. If the number of events actually occurring during the interim analysis exceeds 98 cases, the nominal alpha is adjusted by using the Lan-Demets alpha consumption function of the O' Brien-Fleming boundary to control the I-type errors.
Analysis results in period:
validity results:
the main curative effect index is as follows: results based on FAS subgroup analysis showed that: in addition to the t=1, ecog=0 subgroups, the rectinib group was significantly better than the standard adjuvant chemotherapy group in subjects with disease stage (II/IIIA stage), mutation site (19 del/21L 858R), lobal/total lung excision, pathology type, T-stage (except T1) and lymph node N-stage, smoking history (presence/absence), age (. Gtoreq.65 years, and < 65 years), sex (male/female), baseline ECOG score (except 0).
Secondary efficacy index: based on FAS, the 3-year DFS rates for the icotinib group and standard adjuvant chemotherapy group were 63.88% (95% ci 51.82, 73.67) and 32.47% (95% ci 21.26, 44.16), respectively.
Security results: the security analysis is based on SS. The AE analyzed in summary of the study were only directed to adverse events during treatment.
In SS, the occurrence of AEs in both the icotinib group and the standard adjuvant chemotherapy group were 89.10% vs 97.84%, ADR:76.28% vs 97.12%, grade 3 and above grade 3 AE:10.90% vs 61.15%, AE resulting in suspension of medication: 5.77% vs 9.35%, ADR resulting in suspension of drug administration: 3.85% vs 9.35%, resulting in reduced dose AE:1.92% vs 17.99%, ADR resulting in a reduced dose: 1.92% vs 17.99%, AE leading to withdrawal: 0.64% vs 6.47%, AE leading to withdrawal: 0.64% vs 5.76%, important AE:71.15% vs 87.05%, important ADR:46.79% vs 85.61%, SAE:10.26% vs 17.27%, SAR:1.28% vs 13.67%.
Conclusion:
the Eggetinib vs. EVIDENTE study co-enrolled group 322 subjects is a random control phase III registered clinical test for evaluating the first-generation EGFR-TKI drug with the maximum sample size and maximum standard, which is known at present, and the data robustness is strong from the aspect of test design. The research result shows that the effect of the Icotinib hydrochloride tablet on the postoperative adjuvant treatment of NSCLC patients with EGFR gene sensitive mutation is obviously superior to that of standard adjuvant chemotherapy (vinorelbine and cisplatin or pemetrexed and cisplatin), and the safety is better than that of the standard adjuvant chemotherapy. Taken together, the adjuvant treatment with icotinib provides a safe and effective treatment option for stage II-IIIA NSCLC patients.
The invention has been described in detail in connection with the specific embodiments and exemplary examples thereof, but such description is not to be construed as limiting the invention. It will be understood by those skilled in the art that various equivalent substitutions, modifications or improvements may be made to the technical solution of the present invention and its embodiments without departing from the spirit and scope of the present invention, and these fall within the scope of the present invention. The scope of the invention is defined by the appended claims.

Claims (19)

  1. Use of icotinib or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and/or co-treatment of a patient with a tumor, wherein the patient has been surgically completely resected from the lesion prior to administration of icotinib or a pharmaceutically acceptable salt thereof.
  2. The use according to claim 1, wherein the tumor is non-small cell lung cancer.
  3. The use according to claim 1 or 2, wherein the non-small cell lung cancer is stage II-IIIA non-small cell lung cancer.
  4. The use according to any one of claims 1-3, wherein the non-small cell lung cancer is EGFR mutation positive non-small cell lung cancer.
  5. The use of any one of claims 1-4, wherein the EGFR mutation is an EGFR19 exon deletion mutation or a 21 exon L858R mutation.
  6. The use according to any one of claims 1 to 5, wherein the EGFR mutation is not the 20 exon T790M mutation.
  7. The use according to any one of claims 1 to 6, wherein the patient does not have tumor recurrence or/and metastasis prior to administration of the icotinib or a pharmaceutically acceptable salt thereof.
  8. The use according to any one of claims 1-7, wherein the patient has not received systemic anti-tumor therapy, including chemotherapy, radiation therapy or targeted therapy, prior to administration of the icotinib or a pharmaceutically acceptable salt thereof; further, the targeted therapies include, but are not limited to, monoclonal antibodies, small molecule tyrosine kinase inhibitors.
  9. The use according to any one of claims 1 to 8, wherein the medicament comprises icotinib or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
  10. The use according to any one of claims 1-9, wherein the pharmaceutically acceptable salt of icotinib is icotinib hydrochloride.
  11. The use according to any one of claims 1-10, wherein the icotinib or a pharmaceutically acceptable salt thereof is administered three times daily; preferably, the icotinib hydrochloride is administered three times daily.
  12. The use according to any one of claims 1 to 11, wherein the single dose of medicament is 125mg of icotinib.
  13. The use according to any one of claims 1 to 12, wherein the medicament is administered orally.
  14. The use according to any one of claims 1 to 13, wherein the medicament is a tablet.
  15. A method of treating and/or assisting in the treatment of a patient with a tumor, the method comprising administering to the patient, icotinib or a pharmaceutically acceptable salt thereof, wherein the patient has been surgically removed from the lesion entirely prior to administration of icotinib or a pharmaceutically acceptable salt thereof.
  16. The method of claim 15, wherein the pharmaceutically acceptable salt of icotinib is icotinib hydrochloride.
  17. The method of claim 15 or 16, wherein the tumor is stage II-IIIA non-small cell lung cancer, which is EGFR mutation positive non-small cell lung cancer, which EGFR mutation is an EGFR19 exon deletion mutation or a 21 exon L858R mutation; the EGFR mutation is not a 20 exon T790M mutation.
  18. The method of any one of claims 15-17, wherein the patient does not have tumor recurrence or/and metastasis prior to administration of the icotinib or a pharmaceutically acceptable salt thereof.
  19. The method of any one of claims 15-18, wherein the patient has not received systemic anti-tumor therapy, including chemotherapy, radiation therapy or targeted therapy, prior to administration of the icotinib or a pharmaceutically acceptable salt thereof; further, the targeted therapies include, but are not limited to, monoclonal antibodies, small molecule tyrosine kinase inhibitors.
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