*For medical professionals only
Advanced non-small cell lung cancer (NSCLC) case sharing.
The case, a 57-year-old male, was diagnosed with "right lung cancer (cT3N2M1 stage IV adenocarcinoma), mediastinal lymph node metastases, multiple bone metastases". Initial genetic sequencing revealed a deletion (19del) mutation in exon EGFR19, which progressed after chemotherapy and exetinib treatment. Genetic sequencing again revealed the presence of EGFR mutations combined with MET amplification, and oncitinib + sivotinib (donation) therapy was given, and disease stabilization (SD) was obtained for up to 9 months (until the end of the donation). The case was provided by Professor Ding Haibin of Shaanxi Provincial Cancer Hospital, and Professor Nie Lei of Shaanxi Provincial Cancer Hospital was invited to comment.
Case profile
Fig. 6 Cevotinib was discontinued for 6 months, and chest CT showed tumor enlargement
The case was right lung cancer (cT3N2M1 stage IV adenocarcinoma), mediastinal lymph node metastases, and multiple bone metastases. Initially, an exon deletion mutation was identified in EGFR19. Bevacizumab combined with pemetrexed and carboplatin is given first, followed by bevacizumab + pemetrexed maintenance therapy, the effect is UPPR, and the duration of remission (DoR) is about 10 months.
Treatment with exetinib after disease progression, chemotherapy after disease progression again, short duration of efficacy. According to the results of re-sequencing of genes (EGFR mutation combined with MET amplification), treatment with osimertinib combined with cevotinib for a duration of about 9 months, SD was achieved again, ceaa decreased. After that, due to the interruption of treatment at the end of the cevotinib drug, the disease progressed again, CEA was elevated, cervical vertebrae metastasis, radiation therapy was given to treat local bone metastases, and bevacizumab combined chemotherapy was given again. Currently, treatment is being interrupted due to the outbreak.
Cases are provided by specialists
Professor Ding Haibin: Precision treatment can maximize the benefits of patients
EGFR-TKI is an important treatment for patients with EGFR mutation-positive NSCLC. The CONVINCE study confirmed that in patients with advanced NSCLC with EGFR mutation in mainland China, ecretinib treatment had a significant progression-free survival (PFS) benefit over chemotherapy[1]. The case was treated with exetinib based on the results of the first genetic sequencing.
However, patients treated with EGFR-TKI may develop resistance through various mechanisms, such as acquired EGFR resistance mutations (e.g., Thr790Met), bypass pathway activation (e.g., MET amplification, HER2 amplification, or acquired translocation), or histological transitions (e.g., small cell lung cancer transformation) [2].
For EGFR-TKI-resistant patients driven by MET amplification, MET-TKI combined with EGFR-TKI is an important therapeutic strategy. The TATTON study showed encouraging antitumor activity in patients with advanced NSCLC who progressed after first-, second-, or third-generation EGFR-TKI therapy with MET amplification and EGFR mutations, and the dual-target regimen remained effective after multi-line therapy [2].
After the progression of a generation of EGFR-TKI and chemotherapy therapy, gene sequencing found that EGFR mutations were combined with MET amplification, and the backline was treated with a two-target strategy of cevotinib + osiminib for 9 months, and the efficacy was evaluated as SD. It can be seen that the backline dual-target strategy can allow patients to obtain long-term stable disease control.
In addition, the case was discontinued due to the end of the cevotinib drug donation, and the disease progressed again. If dual-target therapy is continued, patients may receive SD for a longer period of time. In the future, it is hoped that sivotinib will further expand the indications to make it accessible to patients with MET amplification.
It can be seen from this case that in the treatment of EGFR mutation-positive NSCLC, multiple, dynamic genetic testing has important clinical value and significance, and precision treatment can maximize the benefit of patients!
Expert reviews
Professor Nie Lei: In patients with EGFR mutations combined with MET amplification, there is still a benefit of sivatinib combined with osimertinib after multi-line therapy
MET amplification is one of the common acquired resistance mechanisms in EGFR-TKI for EGFR-mutation-positive NSCLC, with a >5% incidence of MET in drug-resistant patients treated with first- and second-generation EGFR-TKI-TKI-resistant patients up to 25%[2]. In the past, most of these patients could only be treated with standard chemotherapy, but the survival benefit was limited, and the use of the backline was greatly limited because of safety issues.
The TATTON study showed that for patients with first/ second-generation EGFR-TKI resistance with MET amplification, the objective response rate (ORR) of sivatinib + oscitinib regimen was 64% to 67%, and the median PFS was about 10 months. Results suggest that the combination of MET+EGFR dual-target therapy remains effective in patients with EGFR-TKI resistance with MET amplification after multi-line therapy.
The patient had previously undergone a variety of treatment options, including a generation of EGFR-TKI and chemotherapy, but the disease control time was short. Disease control is achieved again after treatment with sivotinib combined with osimtinib. During 9 months of taking sivotinib, the disease stabilized, but unfortunately the disease progressed after 4 months of discontinuation of the drug for other reasons. After the treatment experience of this case has fully validated EGFR-TKI resistance, the combination of two-target therapy can bring better survival benefits.
With the listing of cevotinib, the deepening of the understanding of MET, and the success of EGFR-TKI and MET-TKI in many studies, this not only ushers in a accessible treatment option for domestic MET14 jump mutation patients, but also provides a new strategy for the backline treatment of patients with EGFR mutation and MET amplification!
Case review specialist
Professor Nie Lei
Deputy Director of the Second Department of Internal Medicine, Shaanxi Provincial Cancer Hospital
Member of the Chemotherapy Professional Committee of Shaanxi Anti-Cancer Association
Member of the Geriatric Tumor Professional Committee of Shaanxi Anti-Cancer Association
Member of the Bone Tumor Professional Committee of Shaanxi Anti-Cancer Association
Member of the Standing Committee of the Minimally Invasive Treatment Professional Committee of Shaanxi Anti-Cancer Association
He has participated in 2 provincial scientific research projects, participated in the preparation of 2 monographs, and published more than 10 papers in core journals. Since 1997, he has been engaged in the clinical, teaching and scientific research of malignant tumors, adhering to the diagnosis and treatment concept of "not only treating diseases, but also treating people" for malignant tumors, and clinically combining the theory and practice of chemotherapy and targeted drugs to carry out "minimally invasive, low toxicity and high efficiency" personalized treatment for patients with difficult tumors. He specializes in the comprehensive treatment of various malignant tumors.
Professor Ding Haibin
Deputy Chief Physician of the Second Department of Oncology, Shaanxi Provincial Cancer Hospital
Member of the Anti-Cancer Professional Committee of Shaanxi Anti-Cancer Association
Member of the Lung Cancer Professional Committee of Shaanxi Anti-Cancer Association
Member of the Youth Committee of Anti-Cancer Drugs of Shaanxi Anti-Cancer Association
Member of Shaanxi Base of China Medical Education Association
Member of the Shaanxi Provincial Anti-Cancer Association With Multiple Primary And Unknown Primary Tumors
Member of the Grassroots Hospital Working Committee of Shaanxi Anti-Cancer Association
bibliography:
[1] Shi YK, et al. 2016 ASCO Abstract 9041.
[2] Sequist LV, Han JY, Ahn MJ, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study[J]. Lancet Oncol. 2020 Mar;21(3):373-386.
*This article is only used to provide scientific information to medical personnel and does not represent the views of this platform