Conmana (icotinib)

Activation of the Wnt/β-catenin pathway mediates the high expression of PD-L1 to promote the resistance of NSCLC cells to icotinib. Thus, targeted inhibition of PD-L1 expression is of benefit for the treatment of NSCLC.

This review included 23 randomized clinical trials incorporating 7,006 patients and 11 treatments: erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, furmonertinib, aumolertinib, pemetrexed-free chemotherapy (PfCT), pemetrexed-based chemotherapy (PbCT) and placebo. Difference in safety between the third-generation EGFR-TKIs was also first investigated comprehensively. Furthermore, this review elaborated the varied predominate spectrum and ranked the toxicity of EGFR-TKIs for providing toxicity rationale for treatment decisions.

P2, N=40, Not yet recruiting, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.; Peking Union Medical College Hospital, Chinese Academy of Medical Science

P2, N=180, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=30, Not yet recruiting, Jining Medical University Affiliated Hospital; Jining Medical University Affiliated Hospital

These results underscore an additional pharmacological benefit of edicotinib against ABCG2 activity, suggesting its potential incorporation into combination therapies for patients with ABCG2-overexpressing tumors. Further research is warranted to validate these findings and explore their clinical implications.

of the study/trial: ChiCTR-DDD-17013131. Date of registration: 2017-10-27.

P2, N=128, Completed, Sun Yat-sen University | Recruiting --> Completed

P2, N=120, Recruiting, Weihai Municipal Hospital; Weihai Municipal Hospital

A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. Compound b demonstrated slightly improved inhibition activity against PC-9 Del19/T790M/C797S (IC50 = 496.3 nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.

P3, N=251, Terminated, Sun Yat-sen University | Trial completion date: Jan 2023 --> Feb 2024 | Recruiting --> Terminated; Slow accural.

Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.

Compared with adjuvant chemotherapy, adjuvant icotinib may be a cost-effective treatment for resected stage II-IIIA EGFR-mutated NSCLC as the WTP threshold is set at $40 500 per QALY.

P2, N=30, Active, not recruiting, Betta Pharmaceuticals Co., Ltd. | Trial primary completion date: Dec 2023 --> Dec 2024 | Recruiting --> Active, not recruiting

P2/3, N=362, Active, not recruiting, Betta Pharmaceuticals Co., Ltd. | Trial completion date: Dec 2023 --> Dec 2024

No abstract available

P2, N=23, Recruiting, Xue Hou

Erlotinib or gefitinib-treated patients had an overall survival trend that was superior to that of icotinib-treated patients. ASC harboring EGFR mutations can be treated with EGFR-TKI in a similar manner to Adenocarcinoma (ADC) harboring EGFR mutations. There is still a need for further investigation to identify the separate roles of ASC's two components in treating EGFR.

Dacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib. Further research is needed to validate the efficacy of Dacomitinib in this context.

The patient was then treated with icotinib for 8 months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.

DCA demonstrated good clinical prediction effectiveness of the nomogram. Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

In first-generation EGFR-TKIs treatment, gefitinib showed favorable efficacy compared to icotinib and erlotinib, particularly in patients with EGFR L858R mutations...In third-line treatments, the combination of osimertinib and anlotinib demonstrated superior efficacy compared to other regimens. Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) mutation was an independent risk indicator of shorter OS following third-line treatments. Comprehending the tumor evolution in NSCLC is advantageous for assessing the efficacy and prognosis at each stage of treatment, providing valuable insights to guide personalized treatment decisions for patients.

Our case indicated that the feasibility of neoadjuvant icotinib in EGFR-mutant lung adenosquamous carcinoma.

We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

P2, N=82, Recruiting, Abbisko Therapeutics Co, Ltd

As of August 23, 2023, the first generation EGFR-TKIs, gefitinib, icotinib, and erlotinib; the second generation EGFR-TKIs, afatinib and dacomitinib; and the third generation EGFR-TKIs, osimertinib, almonertinib, furmonertinib and befotertinib were all approved for marketing by China National Medical Products Administration (NMPA). In addition, multiple domestic third-generation EGFR-TKIs are undergoing clinical trials, such as rezivertinib (BPI-7711), limertinib (ASK120067), and oritinib (SH-1028). Meanwhile, mobocertinib and sunvozertinib, which targets EGFR 20ins mutations, were also approved by NMPA. With the increasing variety of EGFR-TKIs approved for marketing subsequently, it brings confusion to clinicians when choosing specific medications, and there is an urgent need to develop relevant treatment guidelines. Hence, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists convened experts to integrate the research results of various EGFR-TKIs, and proposed the "China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)", to provide reference for better clinical practice.

The proposed method was used in 100 patients with non-small cell lung cancer for monitoring plasma concentration of the mentioned EGFR-TKIs. The trough concentrations of ICO were distributed between 226.42 ng/mL and 3853.36 ng/mL, peak concentrations were between 609.20 ng/mL and 2191.54 ng/mL. The trough concentrations of OSI were distributed between 110.48 ng/mL and 1183.13 ng/mL. The trough concentrations of GEF were distributed between 117.71 ng/mL and 582.74 ng/mL, while DeGEF was distributed from 76.21 ng/mL to 1939.83 ng/mL with two less than 20 ng/mL. The results of therapeutic drug monitoring aimed to investigate exposure-efficacy/toxicity relationship and improve the efficacy and safety of targeted therapies.

Icotinib combined with radiotherapy can significantly short-term and long-term efficacy of NSCLC patients with brain metastases but not increase adverse reactions.

Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study.

The results were similar when erlotinib or icotinib was compared with gefitinib. Progression-free survival and overall survival for afatinib and dacomitinib were longer than for gefitinib, with small significant differences...Osimertinib is the preferred first-line treatment in patients with advanced EGFR-mutated NSCLC. First- and second-generation TKIs are still considered good options, especially in low-income countries that cannot cover the costs of osimertinib.

Although the efficacy of imatinib in the treatment of chronic myelogenous leukemia in the United States in 2001 was the main driver of protein kinase inhibitor drug discovery, this was preceded by the approval of fasudil (a ROCK antagonist) in Japan in 1995 for the treatment of cerebral vasospasm...One-third of the 21 internationally approved drugs are not compliant with Lipinski's rule of five for orally bioavailable drugs. The rule of five relies on four parameters including molecular weight, number of hydrogen bond donors and acceptors, and the Log of the partition coefficient.

With the extension of treatment duration, there is an observed augmentation in the number of pts experiencing sustained tumor shrinkage and favorable safety of Pimicotinib with no apparent hepatotoxicity. Current data confers durable therapeutic benefits in TGCT pts, suggesting that prolonged exposure may represent an optimal treatment approach. In addition, a separate cohort with prior anti-CSF-1/CSF-1R therapies is underway to assess the safety and antitumor activity.

Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations.

Adjuvant EGFR-TKIs could significantly improve DFS among patients with stage IB lung adenocarcinoma compared with CO, with a safe and tolerable profile.

Among these 59 patients, eight (13.6%) received EGFR TKIs (e.g., afatinib, icotinib, and osimertinib), two patients (3.4%) received IO therapy, eleven (18.6%) initiated platinum-based chemotherapy, fourteen (23.7%) received docetaxel, ten (16.9%) bevacizumab, five (8.5%) paclitaxel, and ten (16.9%) other chemotherapy in the 2nd LOT. The prognosis of advanced NSCLC patients with EGFR ex20ins in China was sub-optimal. The results of this study suggested there is an unmet need of novel therapy for these patients in China.Demographics, treatment patterns, and clinical outcomes of advanced NSCLC patients in ChinaTotal (N=116)Site, %Shanghai60.3Beijing39.7Age, yearMean56.2Median57.6Range27.8 - 76.1Insurance type, %Urban medical59.5Rural medical9.5Smoking status, %Current18.1Previous13.8Non-smoker62.1Cancer stage, %IIIb3.5IVa53.5IVb37.9Not specified5.2Tested for PD-L1, %Positive5.7Negative3.5Unknown74.1Patients with LOTs, %1st LOT1002nd LOT57.8Post-platinum 2nd LOT50.91st LOT (N=116), %Platinum-based chemotherapy85.3EGFR TKI2.6Immunotherapy0.9Other11.22nd LOT (N=59), %Platinum-based chemotherapy18.6EGFR TKI13.6Immunotherapy3.4Other64.4PFS of 1st LOTPFS, median (95% CI)6.2 (5.6, 8.0)Censored, %37.9PFS of post-platinum 2nd LOTPFS, median (95% CI)4.2 (2.7, 5.1)Censored, %25.4Confirmed ORR, %1st LOT14.8Post-platinum 2nd LOT10.0

Patients received 8 weeks of oral icotinib (125 mg thrice daily) plus 2 cycles (3 weeks/cycle) of chemotherapy (pemetrexed 500 mg/m2 and carboplatin AUC5 on day 1), followed by surgical resection. Interim analysis from this study indicated neoadjuvant icotinib plus chemotherapy as an effective and feasible treatment in patients with resectable stage II-IIIB EGFRm NSCLC. The study is still ongoing and final results will be presented in the future.

The patient received icotinib followed by aumolertinib neoadjuvant therapy, achieved significant tumor size shrinkage and downstaging to meet resectability criteria. July 2020, a 58-year-old female patient was diagnosed with right lower lobe adenocarcinoma with stage IIIC (cT4N3M0), accompanied by bilateral lung, hilar, mediastinal lymph node, right supraclavicular lymph node metastasis. This case indicated that initially unresectable advanced NSCLC may transformed into resectable NSCLC through effective TKI-targeted therapy. Neoadjuvant EGFR-TKI in combination to radical surgery may extend postoperative progression-free survival and improved clinical benefits of unresectable advanced EGFR-mutant NSCLC.

Aumolertinib plus icotinib as first-line therapy have significant response rate and a manageable safety profile in EGFR-mutant NSCLC patients with CNS metastases. This study is still in progress and further analyses are warranted to determine longer-term outcomes.

Bilateral choroidal metastases from lung cancer symmetrically are very rare. Icotinib following by almonertinib was an alternative therapy for choroidal metastasis from non-small cell lung cancer with epithelial growth factor receptor mutation.

The evidence provided in this study indicated that the implementation of NVBP policy was related to the expenditure reduction of the first generation of anti-EGFR lung cancer drugs. The policy effectively controlled the increase in expenditures for corresponding drugs while ensuring the use of drugs.

A five-fold cross-validation showed good discrimination with AUC = 0.623. The ABC-score developed in this study was significantly effective as a prognostic tool for icotinib in advanced NSCLC patients with EGFR mutations.