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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Presentations: 1
- Now Available
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
JCSE01.03 - Any Difference on Efficacy and Toxicity Between East and West? (Now Available) (ID 3417)
07:00 - 11:15 | Presenting Author(s): Jie Hu
Any difference on efficacy and toxicity between east and west?
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Lung cancer is now the most commonly diagnosed cancer and the leading cause of cancer related mortality, taking about 1.6 million lives each year. There has been long evidenced that different population display differential sensitivity and safety profiles on different treatment. in addition, many other factors can also influence therapeutic response of patients, such as lifestyle, metabolism, dietary etc. Here we try to explore the impact and underlying mechanism of ethnic difference on response and tolerance of various therapeutic regimens such as cytotoxic chemotherapy, TKIs, antiangiogenic drugs and ICIs.
Treatment patterns of lung cancer has been transformed over the years, leading to the better outcomes of patients. The 5-year overall survival (OS) rate of advanced NSCLC is less than 5% in the standard chemotherapy era. Although widely used of tyrosine kinase inhibitors (TKIs) prolonged progression-free survival (PFS) and OS in patients harboring driver gene mutations, the long-time survival rate was still low due to acquired drug resistance. Over the last five years, emergence of immune checkpoint inhibitors（ICIs）has greatly improved outcomes of NSCLC with objective response rate (ORR) about 20% and 5-year OS rate nearly 16% in previous treated patients based on multiple clinical trials data. A retrospective review of the SEER database found that Asian population presented with higher percentage of metastatic lung cancer but significantly greater overall survival rate among nine different ethnic groups. Furthermore, among the total Asian population, Chinese has the highest percentage of adenocarcinomas (69.4%). The latest data show mutation rate of epidermal growth factor receptor (EGFR) in Adenocarcinoma is 40.3~64.5% and 75% in certain clinically enriched population such as non-smoking adenocarcinoma. These data can fully explain the better outcomes of TKIs in Asia population.
There has evidence that different population has different sensitivity and toxicity to different anti-tumor regiments. Studies showed that hematological toxicities of docetaxel were more frequently observed in Japanese compared to US/European patients. In addition, it is reported that docetaxel-induced grade 3/4 neutropenia is higher in Asian clinical trials than non-Asian trials. On the other hand, the discrepancy of dosage regimen between Japanese (60 mg/m2) and western population implies ethnic difference in PK. Similar data of carbo-platin/paclitaxel and irinotecan-based regimens have been reported in many phase 3 or phase 2 trials.
Meanwhile, there are many studies compared the adverse events of TKIs in different ethnics and data suggested that incidence of ILD caused by gefitinib and erlotinib is higher in Japan (1.2~5.4%) than in the rest of the world.
Despite promising outcomes of ICIs, the clinical trials for Asia population is still rare now. Checkmate 078 was the first trial to predominantly recruit Chinese NSCLC patients, the ORR of Chinese population was 17%, which is in accordance with Caucasian population. However, according to PMS study of Japan and several published meta-analysis results, Asian patients were more likely to develop pneumonitis with the incidence rate 5.7~9.6% in ICIs mono-therapy and these rate would be increased significantly when combined with other drugs. Many genetic studies have revealed the prevalence of genetic polymorphisms (i.e. mutation of SFTPC, ABCA3; telomere-associated genes like TERT, TERC, RTELI, PARN; SNP of MUC5B etc.) was associated with susceptibility to ILD in Japanese. Understanding characteristics of genomic profile will be of no doubt to facilitate the selection of targeted population of ICIs.
Except for the toxicity of ICIs, we should pay attention to the drug response of particular groups of population, which were excluded from clinical trials according to the entry criteria of RCT. Among these HBV-infected NSCLC patients seemed to be more emergency as HBV infected population of Asia is accounted for 62% of global HBV burden, therefore, efficacy and toxicity of ICIs on HBV infected NSCLC patients will be discussed based on many clinical trials or real world data.
In a word, ethnic difference can influence efficacy and toxicity of different treatment options. More genomic mapping and preclinical research should be implemented to explore the relationship between ethnic diversity and varying degrees of response.
Key word: ethnic, efficacy, toxicity, TKIs, ICIs
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