Conmana (icotinib)

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.

The addition of SBRT significantly delayed the onset of acquired resistance to EGFR-TKIs and prolonged the PFS and OS of patients. Radiotherapy of the primary lesion alone might be superior to metastatic sites. Further confirmatory studies are needed to confirm our findings.

This is the largest preclinical/clinical report to highlight that EGFR-K745_E746insIPVAIK and other mutations with exon 19 XPVAIK amino-acid insertions are rare but sensitive to clinically available 1st, 2nd, and 3rd generation as well as EGFR exon 20 active TKIs; in a pattern that mostly resembles the outcomes of models with EGFR-L861Q and EGFR-A763_Y764insFQEA mutations. These data may help with the off-label selection of EGFR TKIs and clinical expectations of outcomes when targeted therapy is deployed for these EGFR mutated lung cancers.

Further subgroup analyses showed that icotinib significantly improved survival in patients with stage III and ECOG score of 1 (HR 0.122, P<0.001). Our nomogram model effectively predicts the overall survival of LAEEC patients, and the benefits of icotinib were found in the clinical stage III population with good ECOG scores.

Befotertinib demonstrated superior efficacy compared with icotinib in first-line treatment for patients with EGFR mutation-positive NSCLC. Although serious adverse events were more common in the befotertinib than the icotinib arm, the safety profile of befotertinib was manageable overall.

P3, N=90, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting

Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR-mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.

For the same patients, the excellent efficacy of bevacizumab combined with erlotinib has been proven in previous studies. The combination of bevacizumab with double-dose icotinib is an effective and relatively safe treatment for advanced NSCLC patients with EGFR L858R mutation. Further exploration will provide more evidence for this type of treatment. Clinical trial information: NCT05263947.

EGFR-TTs evaluated were erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, zorifertinib, and furmonertinib. In the largest cohort of NSCLC LM treated with EGFR TT compiled to date, osimertinib is associated with marginally improved outcomes compared to other EGFR TTs. ECOG performance status is an independent predictor of prognosis in these patients. These results highlight the need for prospective studies for this difficult to treat patient population.

Lastly, the assay was applied to TDM of TKIs in 46 patients and the results were compared to SALLE assisted LC-MS analysis, it could be confirmed that the developed method achieves similarly good results as the already established one and no bias could be detected. It implies that this method capable of supporting clinical follow-up TDM of TKIs in DPS from poor medical environment.

Besides, anti-cancer effects of gallic acid, icotinib hydrochloride, curcumin, ginsenoside Rg3, cryptotanshinone, nitidine chloride, cucurbitacin E, erlotinib, verteporfin, sophoridine, cisplatin and verteporfin in lung cancer are mediated through modulation of Hippo pathway. Here, we summarize the results of recent studies that investigated the role of Hippo signaling in the progression of lung cancer, the impact of non-coding RNAs on this pathway and the effects of anti-cancer agents on Hippo signaling in the context of lung cancer.

Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile. This study was sponsored by Betta Pharmaceutical Co., Ltd.

The observed AEs were consistent with those previously reported. This study is still ongoing and more results will be evaluated in the future, which may contribute to definite the role of dual EGFR TKI therapy in first-line setting.

Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.

We conducted cytotoxicity screening of EGFR mutations on six front-line TKIs based on first-, second-, and third-generation TKIs (afatinib, dacomitinib, osimertinib, erlotinib, gefitinib, and icotinib). We present a comprehensive reference for the sensitivity of EGFR variants to six front-line TKIs. For patients with the EGFR S768I mutation and compound mutations EGFR, six first-line TKIs appear to be reasonable therapeutic options.

P2, N=35, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Phase classification: P3 --> P2 | N=284 --> 35

In this prospective, single arm, phase II study, patients with advanced NSCLC were treated with EGFR-TKI (icotinib 125 mg tid or gefitinib 250 mg qd) for one month followed by SBRT (40-60 Gy/5-8 F/5-10 d) to the primary tumor with concurrent EGFR-TKI until disease progression. There were no Aes equal to or greater than grade 3, with the most frequent AE being radiation pneumonitis. Therefore, administering therapy targeted at the primary tumor using early SBRT after EGFR-TKI initiation is a new potentially safe and effective approach to treat EGFR-mutant advanced NSCLC.

EGFR-TKI targeted therapy can relieve clinical symptoms, and improve immune function and quality of life of patients with advanced NSCLC, which is worthy of clinical application.

Icotinib is safer than gefitinib or erlotinib in the treatment of advanced EGFR-positive NSCLC and seems to bring more clinical benefits to patients. However, there is no obvious advantage in improving the survival rate of patients, and long-term follow-up clinical studies are needed to verify its efficacy.

In 19/55 randomized pts (34.5%) with METamp (GCN ≥5, n=18; MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), median age was 60.4 years, 68.4% were never-smokers, and prior EGFR inhibitors were gefitinib (57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Tepotinib + gefitinib improved PFS and OS vs CT in pts with EGFR-m NSCLC with METamp. INSIGHT 2 is evaluating tepotinib + osimertinib in this setting

Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

The sensitivity of these variants to afatinib, erlotinib, gefitinib, icotinib, and osimertinib was systematically studied by determining their enrichment in massively parallel cytotoxicity assays using an endogenous EGFR-depleted cell line. This study provides a case of deep mutational scanning that simultaneously assayed substitution, deletion, and insertion variants. This approach is applicable for other oncogenes and targeted drugs.