2022 ESMO 丨 Professor Wang Zhijie: Loladinib has a comprehensive and long -term benefit, and Asian patients are also not talking!

*For medical professionals for reading reference

Lolatinib may become the "Almighty King" in the field of ALK -positive NSCLC treatment.

In the 2020 European Academy of Science (ESMO), the results of CROWN's intermediate analysis were amazing [1]. At the annual meeting of the American Cancer Research Society (AACR) this year, CROWN's three -year follow -up results were announced [2]. Subsequently, at the Annual Meeting of the American Clinical Oncology Society (ASCO), which had just ended not long ago, Crown researchers announced the additional 18 months of follow -up data after the mid -term analysis [3], allowing people to see three generations again and again in three generations and time again. Transformation lymphoma kinase (ALK)-Tyidinibicase inhibitors (TKI) -thellantinib.

This year's ESMO Annual Meeting announced a number of CROWN research related analysis data, which analyzed from various aspects such as Asian patients, intracranial efficacy and safety, drug resistance mechanism, and the quality of life of patients. What impact will these research data have on the clinical diagnosis and treatment pattern? What new awareness will we have for Loladinib? The "medical community" was fortunate to invite Professor Wang Zhijie Wang Zhijie of the Cancer Hospital of the Chinese Academy of Medical Sciences to discuss and exchange the above issues.

Lolatini is also "friendly" for Asian patients!

At the 2022AACR annual meeting, the researchers announced the results of CROWN research for three years of follow -up results [2]. This result made targeted therapy for the survival benefits brought by ALK -positive non -small cell lung cancer (NSCLC), reaching an unprecedented new height Essence 63.5%of the 3-yearless survival (PFS) rate (PFS), 83.3%and 72.2%of the intracranial objective relief rate (IC-ORR) and the complete intracranial relief (CR) rate not only enabled the median PFS of ALK-positive NSCLC for the first time For more than three years, it also helped Lolatinini pick up the "crown" in the field of ALK -positive NSCLC treatment.

Asian patients released at the ESMO Annual Conference further proved that Lolatinib can also bring similar excellent effects to Asian patients [4]. Data show that among Asian patients treated with Lolatinib and Kizotinib, the median PFS of the patients is not up to 11.1 months, respectively, and ORR is 78.0%and 57.4%, respectively. Essence

The same is true for patients' intracranial relief. The Loladininib and the Knitininib group patients in intracranial to disease progress (IC-TTP) were not reaching 16.6 months (HR = 0.03, 95% CL 0.004-0.200 To. Among the patients with the base line accompanied by brain metastases, the IC-ORR of the two groups of patients was 72.7%and 20.0%, respectively. In terms of safety, although 79.7%of patients who received Lolatinib were treated with Loladinib, 3-4 treatment related adverse events (Teaes), the incidence of TEAES that caused the suspension of treatment was only 8.5%, and no new safety was found. Signal.

Professor Wang Zhijie said that according to the results of the Crown research released by the researchers for three years, we can see that Lolatini has a strong systemic and intracranial relief ability to ALK -positive NSCLC. According to the data prompts for Asian patients this time, Lolatinib has consistent efficacy and safety of Asian patients as the overall population, and further provides support for the first -line treatment drugs for Asian ALK -positive NSCLC patients.

Take care of the effectiveness and safety, so that patients live and live well!

Another long -term analysis of the intracranial safety and effectiveness of patients in CROWN studies at the ESMO Annual Meeting [5] Tips that the central nervous system (CNS) adverse event (AE) that occurs after the treatment of Lolatinib for treatment occurs after treatment The rate does not increase as the patient's treatment time is extended, and the dosage of Lollainib is reduced due to AE, which may not affect the patient's intracranial efficacy in the short term.

Student data shows that among patients with baselines or patients who do not metastasize, the HR values ​​of the Loladinini group comparison of Ciziidininib groups IC-TTP are 0.10 and 0.02, respectively. Among the 103 CNS AE incidents, 61 cases were relieved without any intervention, and 26 cases were effectively improved by reducing and / or interrupt medications, and 2 cases caused permanent drug suspension. In the statistical patient IC-TTP, it was found that within 16 weeks that reduced the dosage of Lolatinib, the efficacy and dose of it did not reduce the patient. In addition, among patients who received less than 6 months of treatment of Lolatinib, 24.8%of patients appeared CNS AE, and this number was 2.2%among patients who received more than 3 years. The time after the treatment of Latini is prolonged, the incidence of CNS AE will not increase.

Not only that, another study of the quality of life of patients published at the ESMO Annual Conference for the quality of patients in CROWN research [6] shows that whether the patient is accompanied by brain metastasis, Lolatinib can make patients healthy related life life The quality (HRQOL) score is improved. While improving the patient's condition, it can effectively improve the quality of life of patients.

Professor Wang Zhijie pointed out that in addition to the efficacy of drug treatment, the safety of drugs and the improvement of the quality of life brought by patients are also the focus of every clinician and patients. Judging from the data released by researchers this year's ESMO Annual Conference, Lolatinib can also improve the quality of life of patients to a certain extent while taking into account the effects and safety. The huge value played in the field of NSCLC treatment. At the same time, Lolatini may still produce good curative effects while reducing AE, and further enhances clinical confidence in the use of Loladinib. How to provide patients with the best treatment plan for patients?

The problem of drug resistance is the inevitable problem of ALK-positive NSCLC targeted therapy. From the perspective of the drug-resistant mechanism, the drug-resistant mechanism between different Alk-TKI is different. At present, the exploration of the first- and second-generation ALK-TKI drug resistance mechanisms and corresponding strategies is relatively complete, but the drug-resistant mechanism for the three generations of Alk-TKI Lolatini is not yet clear, and it still needs further research. Professor Wang Zhijie said.

A study published by the ESMO conference initially explored the drug -resistant mechanism of Lolatinib [7]. In this study, 27 patients (20%) and 18 patients (13%) patients in the Loladininini group were detected by the baseline CTDNA test, as well as 28 patients (22%) and 23 (18%) patients in the Kizibininini group test. To EML4: ALK variant 1 or 2 (V1/V2) and 3 (V3) mutations; patients carrying EML4-ALK V3 and TP53 mutations are even worse than patients carrying EML4-ALK V1/V2 mutations, but It can still benefit from the treatment of Lolatinib. Among patients with mutations with V3 and TP53, the median PFS of the Lolatinini group is 14.8 months and the Kizotinini group is 5.4 months. At the end of the treatment, 35% of patients in the Lolatininini group detected MAPK, PI3K, and RTK pathways.

In response, Professor Wang Zhijie said that ALK -positive NSCLC is expected to achieve "slow disease" lung cancer subtype. Therefore, clinicians should do a good job of patients' full management work and strive for the best survival of patients. With the continuous development and progress of medicine, the word "precision" has been emphasized clinically. The exploration of the drug -resistant mechanism of three generations of TKI is also an important step in promoting a more complete management strategy. Few and have certain limitations, but also have a certain enlightenment effect on clinical practice. It is hoped that in the future, with the continuous progress of research, it can further discover and solve the problem of drug resistance of the three generations of Alk-TKI, thereby helping ALK-positive NSCLC patients truly achieve precise treatment.

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Expert Introduction

Professor Wang Zhijie

Chief Physician of the Department of Internal Medicine of Cancer Hospital of Chinese Medical Sciences

Published more than 30 SCI papers with communication/first author (including common), including Lancet Resp Med, JCO, Jama Oncol, PNAS, SCI Advs, Cancer Res, Clin Cancer Res, JTO and other magazines.

He was selected as a national "10,000 Plan" youth and a new star in Beijing.

"CSCO Non -small Cell Cancer Diagnosis and Treatment Guide" writer

Member of the National Anti -Cancer Drug Clinical Application Monitoring Committee

Member of the National Cancer Quality Control Center Cancer Cancer Quality Control Commission

Director of the China Clinical Oncology Society (CSCO)

Standing Committee Member of the China Clinical Oncology Society (CSCO) Non -cell Lung Cancer Expert Committee

Standing Committee Member of the China Clinical Oncology Society (CSCO) Youth Expert Committee

Member of the China Anti -Cancer Association Cancer Special Committee

Deputy Chairman of the Youth Committee of the China Anti -Cancer Society of Anti -Cancer Association

Member of the Youth Committee of the Cancer Branch of the Chinese Medical Association

Deputy Chairman of the Cancer Chemotherapy Commission of Human Health and Technology Promotion Association

Deputy Chairman of the Lonopolic Cancer Specialist Committee of China Elderly Health Cancer

The Standing Committee of the China Medical Education Association's difficult tumor committee

Won the second prize of the National Science and Technology Progress Award (third place), the first prize of the "Science and Technology Progress Award" of the Ministry of Education (second place), the eighth Shilan Medical Youth Award, etc.

references:

[1] B. Solomon, T.M. Bauer, F. De Marinis, et al. Lorlatinib vs Crizotinib in the First-Line Treatment of Patients (PTS) with ALK-POSITIVE NOSALLLLLLLLLLLARCRCER (nscl): Phase III CROWN Study [J]. Annals of onCology, 2020, 31 (SUPPL_4): S1180-S1181.

[2] Benjamin Solomon, Todd Bauer, Tony Mok, et al. Updated efficacy and safety from the phase 3 CROWN study of first-line lorlatinib vs crizotinib in advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC )[J]. Cancer Res, 2022; 82 (12_Supplement): CT223.[3] Benjamin J. Solomon, Todd Michael Bauer, Enriqueta Felip, et al. Progression-free survival with subsequent anticancer therapies from a phase 3 trial of lorlatinib In Treatment-Naive Patients (PTS) with Alk+ Advanced Non – Small Cell LUNG CANCER (NSCLC) [J]. Journal of Clinical Oncology, 2022, 40 (SUPPL_16). 9069.

[4] Z. Qing, H.R. Kim, R.A. Soo, et al. Updated analyses from the CROWN study of first-line lorlatinib vs crizotinib in Asian patients with ALK-positive non-small cell lung cancer (NSCLC)[J], Annals of onCology, 2022, 33 (SUPPL_7): S448-S554.

[5] A. Bearz, E. Felip, J. Mazieres, Et Al. Long-Term Intra cover Safety and Effical AnalyseS from the Phase III CROWN Study, Annals of onCology, 2022, 33 (SUPPL_7: Then, then, then

[6] G. Liu, L. IADELUCA, A. Reisman, et al. Health-Related Quality of Life (HRQOL) in Patients with Alk+ Non-Small Cell LUNG CANCER (NSCLC) in The Phase III CROWN Study [J]. Annals of oncology, 2022, 33 (subl_7): S448-S554.

[7] E. Felip, J. Martini, J. Mazieres, Et Al. Resistance Mechanisms to Lorlatinib or Crizotinib in Treatment-Naive Patients (PTS) with ALK+ Advanced Non JlLL LUNCER) Oncology, 2022, 33 (SUPPL_7): S448-S554.

Approval number: PP-lor-chN-0278

Date: 2023-9-15

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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