Professor Zhao Yanqiu: 44%of ORR patients with brain metastases!National Innovation Medicine Schwotini Breaking EGFR 20 outer Xianzi Inserting Classic NSCLC Brain Transfer Curse Curse

*For medical professionals for reading reference

In recent years, with the rise in the incidence of lung cancer, the continuous development of diagnosis and treatment technology has continued to extend the survival time of patients, and the occurrence and diagnosis rate of lung cancer brain metastasis has also increased year by year. Multi -disciplinary comprehensive therapy including surgical surgery, whole brain radiotherapy, three -dimensional directional radiotherapy and systemic therapy is very important for improving the survival of patients with lung cancer and brain metastasis. Compared with EGFR sensitive mutations, EGFR 20 outer appetite insertion (EGFR EXON20INS) mutant -based late NSCLC lacks effective EGFR TKI drugs, and patients with brain metastases are more challenging. At the WCLC conference this year, for the EGFR EXON20INS mutated late NSCLC patients, Schwotinib announced the latest research results: an objective relief rate (ORR) at the RP2D dose is as high as 52.4%, and the patients with brain metastases have shown a good. Anti -tumor activity, ORR reached 44%. The "medical community" was fortunate to invite Professor Zhao Yanqiu in Henan Cancer Hospital to comment on the study.

Like a hardship · EGFR EXON20INS mutant late NSCLC brain metastase patient treatment options for treatment limited

Lung cancer is one of the most common malignant tumors in the world, with a incidence of 22.4/100,000 people/year, and the mortality rate is 18.0/100,000 people/year [1]. About 85%of patients with lung cancer are non -small cell lung cancer (NSCLC). For Asian NSCLC, nearly half of NSCLC patients carry EGFR mutations. EGFR mutations have many subtypes, and different mutations subtypes are different from EGFR tyrosine kinase inhibitors (TKI). Different from EGFR sensitive mutations, EGFR 20 outer plug (EGFR EXON20INS) mutation The existing 1-3 generation EGFR TKI is not sensitive [2-4].

As one of the common modes of lung cancer, about 10%NSCLC patients have brain metastases during diagnosis, and nearly 50%of patients with NSCLC will have brain metastases during treatment [5], and patients with EGFR mutations are more It is prone to brain metastases [6-9], and some studies have shown that 23% -39% EGFR EXON20INS mutant NSCLC patients have brain metastases during diagnosis [10-11]. The prognosis of patients with brain metastases is often poor, and the median survival of patients with unprecedented lung cancer brain metastasis is only 1-2 months [12]. More challenges.

Although the new drugs for the late NSCLC for EGFR EXON20INS mutations in EGFR EXON20Ins have been available in recent years, their curative effect requires a large sample III phase III clinical trial verification, and the efficacy of these new drugs on brain metastases is still very limited. The objective relief rate (ORRRR ) Less than 20%[13]. Therefore, patients with EGFR EXON20INS mutant -type NSCLC need to be more effective and securely targeting new drugs.

Dawn first brings new hope for patients with EGFR EXON20INS mutant lung cancer brain metastasis

As a oral high -selective EGFR TKI, a oral EGFR mutant subtype, in preclinical study of the brain metastlasia lesions in preclinical research (see Figure 1) [14].

Figure 1: In the brain metastases that carry EGFR sensitive mutations or drug resistance, Schwotinib shows a good, dose -dependent anti -tumor activity

Recently, at the 2022 World Lung Cancer Conference (WCLC) held in Vienna, Schwotinib announced the latest research results-three-centered clinical research in domestic and foreign and foreign Summary analysis results [15]: As of April 30, 2022, a total of 119 patients with chemotherapy failed, EGFR EXON20INS mutated late NSCLC patients received Schwotinib therapy and were included in the analysis of the efficacy (the baseline features are shown in Table 1).

Table 1: Effect analysis set (n = 119) Patient's baseline feature; BM: Brain Metastasis, brain metastases;#1 patient (1.2%) data missing

Research results: 84 patients who were treated with Schwotinib RP2D dose (300mg QD) treatment, ORR was as high as 52.4%(as shown in Table 2).

Table 2: Schwotini has anti -tumor activity of patients with EGFR EXON20INS mutations and late NSCLC patients with chemotherapy failure;*: Patients are still undergoing Schwotinib for treatment, and the results of the evaluation of efficacy are to be confirmed; PR: Partial relief; SD: SD: Disease stable; PD: disease progress

It is particularly noteworthy that Schwotinini has a good anti -tumor activity with patients with brain metastases, and ORR reaches 44%, which is surprising (see Figure 2).

Figure 2: The best percentage of the size of the target lesion; AMI: amivantamab; BM: Brain Metastasis, brain metastases

In addition, the overall tolerance of Schwotinib is good, the types of adverse reactions are similar to the traditional EGFR TKI, and there are no special adverse reactions, and most of them are level 1-2, which can be managed and restored in clinical practice. This also means that Schwotini patients with EGFR EXON20INS mutant -variable late NSCLC patients who are accompanied by brain metastases have also taken good on good safety while improving the activity of anti -tumor. Case 1

Basic information: Female, 67 years old, IV -stage NSCLC, EGFR EXON20INS mutations

Treatment: Patients at the end of 2019 in the field of "undercib cancer under the thoracoscopy", postoperative pathological prompt adenocarcinoma, medium differentiation, and genetic testing prompt EGFR EXON20INS mutations; Miticus+Card platinum, Karelizab+Arotinib multi -line treatment progressed. In March 2022, the imaging examination prompts the left brain nodule and the left radiation crown nodule. The left cerebellum transfer stove shooting wave knife SRS, DT22GY/once, tolerance, and in April 2022, it was treated with Schwotinib, and the efficacy assessment PR (see Figure 3). It is still under treatment.

Base line (top) vs. Treatment 3 months (below) after 3 months (below)

Base line (top) vs. Treatment 3 months (below) after 3 months (below)

Figure 3: Before and after the treatment of Schwotinib, the changes in intracranial metastases and lung lesions

Case 2

Basic information: Female, 48 years old, IV -stage NSCLC, EGFR EXON20INS mutation

Base line examination: CT CT can see multiple intracranial metastases, with a maximum diameter of 12.1mm

Treatment: In the past, the disease progressed after the treatment of Pemeter+Card platinum, and after 6 weeks of "Schwotinib 300mg QD" treatment, the intracranial metastatic lesions were significantly reduced (Figure 4).

Figure 4: Schwotinib 300mg QD treatment before and after the treatment of intracranial metastatic lesions

Conclusion

With excellent curative effects and safety, Schobotini obtained China and the United States in 2020 and 2022, respectively, and became the first in the field of lung cancer. "Class I New Drugs" has been carried out globally globally. With the announcement of more research results, it is expected that Schosdinini can bring better survival benefits to more patients with lung cancer, especially brain metastases, and break the spell of the pre -prognosis of the EGFR EXON20INS mutant lung cancer brain metastasis.

Expert Introduction

Chief physician

Deputy Director of Henan Cancer Hospital

Director of the Internal Medicine Internal Medicine 1

Members of the chief expert group of lung cancer and esophageal cancer in Henan Cancer Hospital

Member of the Chinese Anti -Cancer Association esophageal cancer professional committee

Deputy Chairman of Henan Anti -Cancer Association Drug Clinical Research Committee

Deputy Chairman of the Henan Provincial Anti -Cancer Association Cancer Molecular Medical Committee

references:

[1] .Cancer today. Global Cancer Observator. Https://gco.ik.fr

[2].Jacqulyne P Robichaux, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nature Medicine. 2018 May;24(5):638-646

[3] .piotrowska Z, et al. ECOG-Acrin 5162: A Phase II Study of Osimertinib 160 mg in NSCLC with EGFR EXON 20 Insertions.j Clin Oncol 2020; 38 (SUPPL): Abstract 9513

[4] .Guang Jian yang, et al. Osimertinib for Chinese Advanced Non-Small Cell LUNG CANCER PARBORONTS HARBORONG DIVFR EGFR Exon Mutations. 2021; 152: 39-48

[5]. Wen Ouyang, et al. Metachronous Brain Metastasis in Patients with EGFR-Mutant NSCLC Indicates a Worse Prognsis. J CANCER. 2020; 11 (24): 7283-7290.

[6] .dagogo-jack I, et al. Treatment of Brain Metastases in the Modern Genomic Era. Pharmacol theer.2017; 170: 64-72. [7] .tao jiang, EGFR TKIS Plus WBrtodaStrated No So So So So So So So So So So So Soomonstrad Benefit Other than that of tkis alone in patients with nsclc and EGFR Mutation and Brain Metastases.

[8] .min yb, et al. The korean association of interzard media.2016.online

[9] .hsu f et al. EGFR Mutation Status on Brain Metastases from Non-Small Cell LUNG CANCER. LUNG CANCER. 2016; 96: 101-107

[10] .Cardona Af, et al.egfr Exon 20 Insertion in LUNG ADENOCARCINOMAS AMONG HISPANICS (Geno1.2-CLICAP). LUNG CANCER 2018; 125: 265–72.

[11] .YANG G, et al. EGFR EXON 20 Insertion Mutations in Chinese Advanced Non-Small Cell LUNG CANCER PATIENTS: Molecular Heterogeneity and Treatment FROM National-World Stud.

[12] .won yk, et al. StereotActic Radiosurgery for Brain Metastasis in non-Small Cell LUNG CANCER. Radiat OnCol J. 2015; 33 (3): 207-216.

[13].Pasi A Jänne, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion-positive metastatic non–small cell lung cancer: Treatment beyond progressive disease in platinum-pretreated patients with and without intracranial PD.2022 ASCO abstract 9099

[14] .Yan xu, et al. DZD9008, An ORAL, Wild Type Selective EGFR Inchibitor Forthe Treatment of Non-Small-Cell LUNG EXON20 Inseer Mutations.

[15] .j.c-h. Yang, et al. Sunvozrtinib in NSCLC Patients with EGFR EXON20 Insertion Mutations. 2022 WCLC Abstract EP08.02-029

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