The emergence of targeted therapy has brought a new treatment model of high efficiency and low toxicity to non-small cell lung cancer (NSCLC), especially improving the efficacy and survival of patients with advanced NSCLC. With the continuous deepening of targeted therapy research, many effective NSCLC treatment targets have emerged, such as EGFR, ALK, RET, MET and ROS1. For a more comprehensive understanding of NSCLC targeted therapy, today
The application of targeted drugs with HER2+, KRAS mutation and NRG1 gene fusion in the field of NSCLC was reviewed.
HER2+ mutation-related targeted drugs
Her2 targets have been found in the NSCLC field for a long time and have achieved certain efficacy, but the overall situation is not satisfactory. At present, the therapeutic drugs for this target mainly include afatinib, trastuzumab, lapatinib and so on. The latest results of the IFCT-1703 R2D2 study, which analyzed the effects of a triptych of trastuzumab + patuzumab + docetaxel in the treatment of patients with advanced non-small cell lung cancer with HER2 mutations, were presented at the 2021 ASCO conference. The results showed: (1) The triple regimen showed good anti-tumor activity, with an overall response rate (ORR) of 28.9% and a disease control rate (DCR) of 56%; (2) The median duration of remission (DOR) was 11.0 months, and progression-free survival (PFS) and overall survival (OS) were 6.8 months and 17.6 months, respectively, as detailed in the figure below.
It is also worth noting that there was a study (abstract 9035) at the 2021 ASCO conference that applied the pan-ErbB inhibitor parotinib + apatinib to treat patients with her2 amplification or mutation in metastatic non-small cell lung cancer, and showed good anti-tumor activity, showing that: (1) the overall response rate (ORR) reached 45.5%, and the disease control rate (DCR) was 93.9%; The median progression-free survival (PFS) was 6.8 months, the median duration of remission (DOR) was 5.3 months, and the median overall survival (OS) was 12.9 months. (2) Regardless of whether the patient has brain metastases or above the second line of treatment, the combination therapy can maintain a high level of efficacy.
KRAS mutation-related targeted therapy
The incidence of KRAS mutations in patients with NSCLC is about 25% to 33%, which is one of the common genetic mutations, so if targeted therapy for KRAS mutations can be carried out, its therapeutic significance for patients with NSCLC is very great. Among targeted therapies for KRAS mutations, Sotorasib is a very noteworthy targeted drug, achieving an effective response rate of approximately 54%. The latest findings of the Code Break100 study, published at the 2021 ASCO conference (published in the journal NEJM), a global, single-arm, Phase II clinical study designed to evaluate the efficacy and safety of sotorasib (oral, twice daily, 960 mg) in patients with locally advanced or metastatic KRAS G12C mutation NSCLC. A total of 126 patients with the above NSCLC were enrolled, and at least 1 dose of sotorasib was treated, with a median follow-up of 15.3 months, and the results showed that: (1) receiving sotorasib treatment could achieve an objective response rate (ORR) of 37.1% in patients with KRAS mutation NSCLC, 6.8 months in progression-free survival (PFS), and 12.5 months in zhang wei's overall survival (OS).
Targeted therapy related to NRG1 gene fusion
NRG1 gene fusion is detected in about 3% of non-small cell lung cancers (NSCLC), which generally bind to the HER3 gene. The new drug zenocutuzumab (MCLA-128) is a her2/HER3 dual antibody drug that plays a role in the treatment of NSCLC with NRG1 gene fusion. eNRGy is a Phase I/II study that included patients with tumors with NRG1 gene fusion, including pancreatic cancer, non-small cell lung cancer, and other types of solid tumors, all of whom received zenocutuzumab 750 mg every 2 weeks. Results In 2021, asCO updates, the objective response rate (ORR) of Zenocutuzumab for tumor patients with NRG1 fusion reached 29%, of which the ORR of NSCLC patients with NRG1 fusion was 25% (see the figure below), and the overall adverse reactions were controllable.
brief summary
Targeted therapy is of great significance to NSCLC treatment, and continuous exploration and discovery of effective targets and related drugs for NSCLC treatment will continuously improve the efficacy and long-term survival of NSCLC patients. Among them, HER2+, KRAS mutation and NRG1 gene fusion are more important changes in NSCLC, and the research on related treatments is extremely valuable, and it is hoped that with the continuous advancement of research, more low-toxicity and efficient targeted treatment programs can be brought in the future.
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