Professor Zhao Mingfang: Dakortini has its own characteristics and advantages, strengthen the understanding of drugs and toxicity management, is expected to help patients achieve high-quality long-term survival

In May 2019, the second representative of the thin growth factor receptor tyrosine kinase inhibitor (EGFR TKI) Dacostini was officially approved in China, becoming the first-line treatment option for patients with advanced non-small cell lung cancer (NSCLC) with eGFR gene sensitivity mutationIn nearly 1 year of clinical practice, Dacostinib has shown good efficacy and safetyDacostinib has its own characteristics and advantages, strengthen the awareness of drugs and toxicity management, is expected to help patients achieve high-quality long-term survival
Dacostinib has been listed in China for nearly a year, many patients have also received Dacostini treatmentBut in previous clinical studies, has been criticized by everyone is that the toxic side effects of Dacostini are large, so many grass-roots clinicians, patients are a little afraid of DakotaBecause of the lack of awareness of Dakatinib, we are not as comfortable in clinical applications as other EGFR TKIthe current EGFR TKI has been "three generations of the same room", each drug has its own advantages and disadvantagesWe must develop individually precision treatment for patients on the basis of standardized treatment, in accordance with the specific conditions of patients, combined with the clinical characteristics of the drug, especially pharmacokinetic seticing characteristicsEach drug has its applicable population, how to maximize the efficacy of the drug, while controlling to the smallest toxic damage, so that patients can have a high-quality survival opportunity, clinicians should pursue the ultimateDacurini has its unique advantages, the ARCHER 1050 study of the clinical data is also very beautiful, reached the main end of the non-progressive survival (PFS) study, and in the total survival (OS) also has a more significant extension, especially in the Chinese group, the efficacy of Darbutini first-line therapy (PFS) more than 18 monthsIn clinical applications, we should make full use of the efficacy advantages of Dacotinib, but also to avoid its toxic side effectsthe toxic side effects of dacotinib are closely related to their mechanism of actionDacutinib is a pan-HER inhibitor, which inhibits HER1, HER2 and HER4, which means that its toxicity to epithelial cells is particularly obvious, thus showing common adverse reactions such as rash, dry skin, enteritis, stomatitis, diarrhea, etcThe maximum tolerable dose of dacostinib is applied in clinical studies, and dose adjustment in clinical practice enables patients to maximize their benefits with minimal toxicityThe retrospective results also showed that patients with better tolerance after the dose of dacostinib were reduced, with no effect on the effect, or even better than the maximum tolerable dose group In this case, in terms of mechanism of action, dacostinib may have an advantage in patients with combined mutations or EGFR amplification, or HER2 mutations In addition, for patients with EGFR gene sensitivity mutation, Daoctini benefited more from the EGFR gene 21 exon L858R mutation population Therefore, as long as in clinical practice to do a good job of dabutinib toxicity management, patients have a good chance of long-term survival the current lung cancer has gradually slowed down, some patients can achieve long-term survival, on this basis, we also want to pursue high-quality survival for patients Therefore, in clinical practice, we must carry out a reasonable population division, so that each drug can play to the extreme From the point of view of pharmacokinetics, dacurinib has a longer half-life, 1 time per day orally, and reduces the amount of toxicity management without reducing the effect For the more "invisible" toxic reactions such as liver toxicity, cardiac toxicity and interstitial lung injury, the experience of early patients is often not as obvious and profound as rash and diarrhea, but in fact, of all EGFR TKI, Dacostinib has the smallest proportion of the above toxic reactions The review and analysis also showed that the incidence of adverse reactions at level 3 was very low after the dose reduction of dabutinib, and there were almost no adverse reactions of more than 4 levels So to do a good job of toxicity management, Dacardiini hopes to get more patients to achieve long-term survival Especially for this particular group of young patients as the backbone of the family, we should allow Dacotinib to take full advantage of this drug the clinical operability and patient compliance is higher
the current first, second and third generation EGFR TKI are the first-line treatment options for patients with advanced NSCLC of EGFR gene sensitivity mutation, how should we screen the population to apply the most suitable drugs? Combined with clinical practice, I think that should not only meet the EGFR single gene testing, in the scope of reach, we should try as much as possible for patients to carry out high-volume multi-gene testing, so as to better control personalized precision treatment, but also better guide the choice of drugs Of course, high-throughput genetic testing has not yet been included in the national health insurance, and our China Medical University affiliated with the First Hospital has 10 gene testing into the health insurance, so for the first treatment of patients, we will be preferred to be covered by the genetic testing products covered by health insurance after testing, need to be based on the results of genetic testing population division, if the EGFR gene 19 exogenous missing mutation patients, the choice of drugs is more extensive, as long as the patient's basic state and comorbidities can choose the appropriate drug; For this type of patient, we recommend the second-generation drug dabutinib as a priority In addition, Dacostinib needs to accumulate more clinical data for the treatment of rare and co-mutations, and dacostinib is a pan-HER inhibitor in terms of mechanism of action, which may have better efficacy for patients with combined mutations also noteworthy is that many drugs are developed very quickly, in order to pursue the best efficacy to get through the fast approval channel, clinical research often at the expense of drug safety and the pursuit of maximized near-term efficacy Once the drug is available, it is our clinician's responsibility to help patients select the best dose of the drug for clinical treatment, a real-world dose of the treatment we call the best biological therapy effective dose Many cancer drugs today pass the most resistant dose slots, but there is actually plenty of room for regulation For example, Dacotinib, the initial dose currently used in our general clinical application is 30 mg, based on 1 month's evaluation of efficacy and patient tolerance to consider whether the need to increase the dose The study reported that after the patient was reduced from the 45mg starting therapeutic dose to 15mg, the patient's efficacy was not affected and toxicity management was very good However, in our clinical practice, patients did not experience 30mg intolerance and reduced to 15mg from The market in May 2019 to the present, in my clinical practice, the treatment of Dakota tinney as a first-line treatment of patients, there has not been a case of disease progression, the overall toxic reaction is mainly rash, mainly a level 1 reaction, diarrhea is relatively not serious Of course, some patients can reach level 2 of stomatitis, but by reducing or stopping the drug can be quickly restored, generally the toxic reaction of dacostinib basically occurs within 2 months, and then will be tolerated soon, and there is no more than 3 adverse reactions Therefore, as long as the dose of the drug is adjusted well, the clinical operability of Dacurinib and patient compliance will be very good In addition, in terms of hepatophandtoxicity, no case of liver dysfunction has been found in the course of treatment, so for patients with underlying liver disease, the same priority can be given to receiving dacostinib treatment the data in the real world is equally valuable, looking forward to the exploration Dacostini was approved for listing in China for nearly a year, clinical practice shows that Dacostinib's toxicity can be controlled, safe and sound, expect more patients in the future from Dacostini's treatment to achieve high-quality long-term survival For the EGFR gene 21 exon L858R mutant population, the real world to receive the efficacy of dacostinib treatment is consistent with clinical research, is our real world worth exploring point, but also hope that clinicians can work together to explore the efficacy of Dakota tinney in special population, and real-world research data are also very valuable good efficacy data, in terms of safety, although two-thirds of the patients in the ARCHER 1050 study need to be dose-adjusted, in fact, the toxic reaction of dacostinib causes only about 10% of patients to stop the drug, which is comparable to the first-generation drugs (7-8%) and third-generation drugs (13%) ( 6), so there is no need to worry too much The toxicity of Dacutinib is mainly reflected in the damage of the skin mucosa, which is easy to control clinically and can significantly reduce its incidence by reducing the dose In addition, it is worth reminding that for EGFR TKI, the amount may not be the best dose, we do not have to be too strong 45 mg this sufficient starting dose, can consider starting from 30 mg, so that the dose of subsequent treatment can be increased or decreased, more at ease In personal practice, it is also very safe for some elderly patients to apply a 30 mg starting dose overall, through reasonable toxicity management, Dacostinib can play the best effect in patients while minimizing toxicity, so that patients really get long-term survival In addition, there is an opportunity to choose a third-generation drug after Dacostinib treatment, and if a third-generation drug is chosen, subsequent treatment options can be difficult Judging from the available data, Dacotini does have its own advantages by Zhao Mingfang Source: