The European Association for Oncology Asian Annual Meeting (ESMO ASIA) is sponsored by the European Association for Oncology and is a leading platform for Asia-Pacific to discuss the latest data and breakthroughs in the field of oncology. ESMO ASIA 2022 will be held in Singapore in an online + offline format from December 2-4. This article compiles five latest progress announced by the Chinese research team in the field of targeted lung cancer treatment at this year's ESMO ASIA conference. Details are as follows:
retrospective study: Vometinib is used for EGFR mutation
NSCLCh Postoperative adjuvant treatment
Vometinib is a new third-generation EGFR-TKI that can target EGFR-sensitive mutations and EGFR T790M mutations. Previous trials have shown that vometinib has shown encouraging efficacy and good tolerance in advanced non-small cell lung cancer (NSCLC). At this year's ESMO ASIA conference, a Chinese research team released a retrospective analysis that evaluated the efficacy and safety of vometinib in postoperative adjuvant treatment in patients with EGFR mutation NSCLC.
Methods
study included patients with EGFR mutation who underwent radical lung cancer surgery, and patients received 80 mg of vometinib daily. The duration of adjuvant treatment (up to 3 years) depends on the patient's pathological stage and physical condition. The study also evaluated the disease-free survival (DFS), safety, tolerability and efficacy of vometinib in patients with mixed ground glass shadow (mGGO) lesions.
Results
This study retrospectively analyzed 106 patients with stage IA2~IIIB NSCLC who were pathologically confirmed to be adenocarcinoma, EGFR mutation positive (19 exon deletion, L858R, 20 exon insertion mutation or G719A mutation). All patients were followed up for at least 6 months, and 47 patients were followed up for more than one year, with a median follow-up time of 11.0 months. When the data ended on July 1, 2022, all patients were still alive and no patients relapsed. During the treatment period of
, treatment-related adverse events (TRAEs) occurred in 33 patients (33/106, 31.1%), and 2 patients (2/106, 1.9%) had TRAEs of grade 3 and above. The most common TRAEs were rash (19/106, 17.9%), diarrhea (9/106, 8.5%), fatigue (6/106, 5.7%) and elevated aminotransferase (5/106, 4.7%). One patient (1/106, 0.9%) stopped treatment due to adverse events.
This study also evaluated the efficacy of vometinib in patients with mGGO. Among 35 (35/106, 33.0%) patients with mGGO lesions after surgery, 17 (17/35, 48.6%) were reduced.
Safety Analysis
1, 2 patients CT chart
Conclusion
vometinib was used for EGFR mutation after radical lung cancer surgery. NSCLC patients showed good efficacy and acceptable safety. In addition, vometinib also showed initial efficacy in patients with mGGO lesions.
ACHIEVE study: The efficacy of high-dose ametinib in the first-line treatment of EGFR mutations with EGFR mutations in
ACHIEVE (NCT04808752) is an ongoing multi-center, open-label, single-arm study aimed at evaluating the efficacy of high-dose (165mg) third-generation EGFR-TKI ametinib in the first-line treatment of EGFR mutations and EGFR-TKI. At this year's ESMO ASIA conference, Professor Fan Yun's team at Zhejiang Cancer Hospital released ACHIEVE research and analysis data.
Methods
study included patients with EGFR-sensitive mutations confirmed by histology or cytology . Patients with asymptomatic brain metastasis, stable central nervous system (CNS) metastasis were allowed to enroll for at least two weeks. The enrolled patients received ametinib treatment (once a day, oral, 165 mg). Study endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), CNS ORR, and CNS DCR.
results
When the data ended on July 4, 2022, 22 patients were included in the analysis. The median follow-up time was 4 months. At the end of the data, 20 patients were still receiving treatment, with median age 61 years (48-75 years), 63.6% were female, and all patients had measurable CNS lesions during baseline brain scans. Overall ORR was 90.9% (20/22; 95% CI: 70.8-98.9). CNS ORR was 86.3% (19/22; 95% CI: 65.1-97.1). Overall DCR and CNS DCR were 100%.
efficacy analysis
patients experienced elevated serum creatine kinase (CPK), and the ORRs of patients with or without CPK elevation were 100% (5/5) and 88.2% (15/17; 95% CI: 63.6-98.9), respectively. ORR
from baseline target lesions The data is not yet mature. The safety results of ametinib are consistent with previous studies.
Conclusion
ametinib (once a day, 165mg) showed initial good efficacy when used in the first-line treatment of patients with EGFR mutation brain metastasis NSCLC. Relevant registration trials will continue.
High-dose ametinib has poor efficacy in patients with EGFR mutations
NSCLC. At this year's ESMO ASIA conference, a Chinese research team announced the efficacy and safety of ametinib in patients with rare EGFR mutations NSCLC.
Method
study included patients with non-squamous NSCLC with rare mutations in stage IIIB-IV EGFR, and ECOG PS was 0-1, and patients with asymptomatic CNS metastasis were allowed to enroll. 40 patients were included in the 20 exon insertion mutation (cohort 1) and other EGFR rare mutations (cohort 2) cohorts with non-exon insertion mutations, respectively. The enrolled patients received monotherapy of ametinib (165 mg, oral, once daily). The primary end point is ORR.
Study Design
Results
021 to May 20 patients were included in cohort 2. 16 patients were subjected to imaging evaluation. At this conference, the researchers only published the results of the relatively mature cohort 2. In queue 2, the ORR is 50% and the DCR is 100%. In the genotype subgroup analysis, the ORRs of patients with G719X & L861Q & S768I and other genotypes were 53.8% and 33.3%, respectively. The mutations of G719X, L861Q, and S768I were 8, 6 and 1 cases respectively, and the other mutations included L747P/S, V774M, H773M, etc.
efficacy analysis
from baseline target lesions best relieved
1 patients experienced elevated creatine kinase (CK). Subgroup analysis of patients with elevated CK showed that ORRs of 0, 1-2 and 3 or higher were 40%, 50%, and 57.1%, respectively. Three of the patients used coenzyme Q10 to reduce CK. The median duration of Coenzyme Q10 treatment was 3 months, with an average reduction of CK by 63%. Conclusion
high dose ametinib is effective in NSCLC patients with rare EGFR changes except for 20 exon insertion mutations. The latest data show that elevated CK is positively correlated with the efficacy of ametinib. Compared with other genotypes, ametinib is more effective in patients with G719XL861QS768I mutation.
ametinib sequential SRT was used for intracranial oligometastasis
NSCLC preliminary study results
ametinib has better efficacy in intracranial lesions than in the first generation EGFR-TKI. Stereodirectional radiation therapy (SRT) is highly effective and low toxic for a limited number of intracranial metastases. Studies have shown that existing lesions are likely to occur before new distant metastasis, so more effective local treatment (including SRT) after first-line EGFR-TKI progression may benefit patients. This study aims to evaluate the efficacy and safety of ametinib sequential SRT in patients with intracranial oligometastatic NSCLC.
Methods
study included patients with intracranial oligometastatic treatment in EGFR-TKIs. The patient received 110 mg of ametinib daily until the progression of intracranial disease. If possible, SRT (32–40 Gy, 8 Gy/f in total) is continued for intracranial oligomerization progression disease. The primary endpoint was the objective intracranial remission rate (iORR). Secondary endpoints included intracranial progression-free survival (iPFS), duration of intracranial remission (iDOR) (as per RECIST1.1 standard); brain radionecrosis rate (CRNR), and overall survival (OS). Adverse events were evaluated according to the Standard for Common Adverse Events General Terminology Version 5.0 (CTCAE v5.0).
Research Design
Results
As of June 22, 2022, a total of 8 patients were enrolled: 3 males and 5 females; the follow-up time ranged from 3 months to 12 months. All 8 patients received only 110 mg ametinib per day. All lesions (intracranial and extracranial) achieved partial remission (PR). iORR is 100%. No patients are currently required to receive SRT. No adverse events of level 3 or above occurred.
Conclusion
This is the first study of patients with intracranial oligometastatic NSCLC receiving sequential SRT. Ametinib showed initial efficacy and good tolerance in intracranial oligometastatic EGFR mutation NSCLC. The study is underway and further results are expected to be released in 2023.
CTONG1702 and 1705: Preliminary results of first-line pyrrolitinib in patients with
HER2 mutation advanced NSCLC released
CTONG1702 study is an open-label, multi-center, multi-cohort phase II umbrella clinical study aimed at evaluating the efficacy and safety of pyrrolitinib in patients with initial treatment of HER2 mutation NSCLC. At the same time, the researchers also conducted an observational and real-world study as a control (CTONG1705). At this year's ESMO ASIA conference, the team of Professor Wu Yilong, Professor Li Yangqiu, Professor Zhou Qing and Professor Liu Siyang announced a parallel, multi-center, multi-cohort patient individualization study (CTONG1702 and 1705): exploring its feasibility and the efficacy and safety of first-line pyrrolitinib in the treatment of patients with advanced HER2 mutation NSCLC.
method
This study consists of a simultaneously initiated open-label phase II umbrella trial CTONG 1702 and a real-world study CTONG 1705. Untreated advanced NSCLC patients were screened through second-generation sequencing technology (NGS). Eligible patients with HER2 mutations were included in the study, and the enrolled patients received 400 mg of pyrrolitinib (oral, twice daily) until the disease progressed or unacceptable toxicity appeared. Patients with HER2 mutation who did not receive pyrrolitinib in clinical practice were included in the CTONG1705 study.
Results
study screened 932 patients, 28 patients with HER2 mutation met the enrollment conditions and were included in the CTONG1702 cohort, and 8 patients with HER2 mutations were included in the CTONG1705 cohort.
Flowchart
When the data ended on December 1, 2021, the median follow-up time was 16.5 months, the ORR of pyrrolitinib in the CTONG1702 study cohort was 35.7%, the DCR was 89.3%, and the median PFS was 7.3 months.
efficacy analysis
CTONG1705 study cohort received routine treatment first line: 2, 4 and 2 patients received chemotherapy, immunotherapy and targeted therapy, and no patients achieved PR, and the DCR was 75%. The median PFS was shorter in patients receiving routine treatment (3.0 months) compared with pyrrolitinib (P=0.049).
Tumor remission and persistence in patients with HER2 mutations treated with pyrrolitinib (waterfall/swimming pictures)
CTONG1702 study cohort, the most common TRAEs were diarrhea (87.5%), rash (32.1%) and elevated AST (25%). The incidence of grade 3 TRAE is 10.7%. No patients had grade 4 or grade 5 adverse events.
Conclusion
pyrrolitinib shows good efficacy and low toxicity in patients with HER2 mutation NSCLC. It is a potential and clinically significant treatment option and may be better than conventional treatment options.
Reference source:
[1] 299P - Furmonertinib as adjuvant theraPy in EGFR-mutated non-small cell lung cancer following radical lung cancer surgery.2022 ESMO ASIA.
[2] 367P - High-dose aumolertinib in EGFR-mutant NSCLC Patients with brain metastases: Primary data from ACHIEVE.2022 ESMO ASIA.
[3] 373P - Safety and efficiency of aumolertinib treatment in Patients with advanced NSCLC harboring uncommon EGFR mutations: Cohort 2.2022 ESMO ASIA.
[4] 375P - Stereotactic radiotheraPy (SRT) in combination with aumolertinib to treat intracranial oligometastatic non-small cell lung cancer (NSCLC): A Phase II, ProsPective study. 2022 ESMO ASIA.
[5] 385P - Efficacy and safety of Pyrotinib in untreated, advanced non-small cell lung cancer with HER2 mutations: A Parallel, multi-center, multi-cohort Patient-centric study (CTONG1702 and 1705).2022 ESMO ASIA.
Editor: Yuna
Type: Yuna
Execution: Babel
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