Lung cancer can be said to be a malignant tumor that is difficult to treat at present, and it is also a tumor that is more studied in the medical community. Many lung cancer patients also experience several targeted therapies or chemotherapy resistance during treatment. For patients with lung adenocarcinoma, the probability of EGFR mutations will be greater, and targeted therapy is a treatment method with better treatment effect and more convenient treatment. Most patients will also face such a situation, the use of osimertinib after the appearance of EGFR mutations, but after a few months of re-examination, the lesions have increased again, many patients will be more worried, what is the reason for this? Next, let's understand the use of osimertinib and what is the mechanism of drug resistance?
For lung cancer patients, the survival time of EGFR positive will be longer, as a new generation of targeted drugs osetinib effect and resistance mechanism is what is the mechanism?
A Danish cohort study analyzed morbidity and mortality of EGFR mutations in patients with IB-IIIA NSCLC. In the study, 5478 patients with IB-IIIA NSCLC were included, and among patients with EGFR mutations, 64% underwent surgery, 29% received postoperative adjuvant chemotherapy and/or radiotherapy, 41% received radiotherapy, and 58% received radiation therapy, and the 5-year mortality rate of patients with EGFR mutations was numerically lower than that of EGFR-negative patients. Among them, the 5-year mortality rate of EGFR mutation and negative people who underwent surgery was 23% vs 25%, and the number of people who did not undergo surgery was 45% vs 54%. This suggests that the survival prognosis of different types of patients with NSCLC is also different, and perhaps the application of subsequent targeted therapy has a certain impact on the relative prolongation of survival time of patients with EGFR mutations.
For EGFR-positive patients, targeted therapy can relatively prolong the survival of patients, and there are also first-line, second-line, and third-line targeted drugs, such as Iressa, Trokai, alfatinib, osimtinib, and so on. A systematic retrospective analysis included five studies (998 patients) analyzing the efficacy and safety of osimertinib vs. generation EGFR-TKI in the first-line treatment of advanced NSCLC with EGFR mutations. The results showed that the efficacy of osimitinib was better than gefitinib/erlotinib, and its safety was good despite the longer duration of drug exposure to osimitinib. The study concludes that osimtinib should be the preferred first-line treatment regimen for patients with advanced NSCLC mutations in EGFR. In August 2019, oscitinib was approved for first-line treatment in adult patients with locally advanced or metastatic NSCLC who have a positive EGFR gene mutation.
But many patients who take osimertinib will also find that after about a year of use, drug resistance will occur, and the tumor will enlarge again.
An observational, multicenter study included 82 patients using osimertinib first-line treatment of advanced NSCLC with EGFR mutations to assess the pattern of progression and safety following oshitinib resistance. The results showed an ORR of 68.3%, a disease control rate (DCR) of 86.6%, and a median PFS of 22 months. A total of 5 patients were detected with mechanisms of resistance that can be targeted therapy, including MET amplification (3 cases), MET amplification/EGFR amplification (1 case), and HER2 amplification (1 case).
The above is an introduction to the use of osimertinib and the mechanism of drug resistance, but whether it can be used, it is also necessary to conduct genetic testing first, and ask the doctor to evaluate the detailed treatment plan. Related studies have shown that 50% of patients convert from PD-L1 <1% to PD-L1 after treatment with osimertinib≥1%, and 20% of patients convert from PD-L1 < 20% to PD-L1≥20%. This means that patients can also use immunotherapy to continue to control the disease. With the advancement of medical technology, targeted combination therapy, immunotherapy, etc. can be used as the consideration direction of follow-up oscitinib resistance, and there are more clinical trials in the clinic, which also makes us look forward to more and better efficacy and treatment options.