Current clinical practice and physicians’ insights on Chinese patients with advanced non-small cell lung cancer habouring epidermal growth factor receptor 20 insertion mutation
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ABSTRACT:
SUBMITTER: Shi Y
PROVIDER: S-EPMC11342509 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Platinum-based chemotherapy was previously the first-choice treatment for lung cancer. The discovery of epidermal growth factor receptor (EGFR) gene mutations and the development of EGFR tyrosine kinase inhibitors (TKIs) marked the beginning of the targeted therapy era for non-small-cell lung cancer (NSCLC). Thirty percent of NSCLC patients carry EGFR gene mutations. For these advanced NSCLC patients, EGFR-TKIs are currently preferred for their superior activity and survival benefits over platinum-based chemotherapy. However, therapeutic efficacy is quite different in patients with EGFR exon 20 insertion (ex20ins) mutations versus common mutations. Patients with ex20ins mutations are insensitive to EGFR-TKIs and have poor prognosis. Some drugs targeting EGFR ex20ins mutations have been approved. Here, we systematically reviewed the recent clinical research of and treatments used for EGFR ex20ins mutations, summarized the latest data on emerging therapies, and discussed future prospects and treatments.
| S-EPMC9008900 | biostudies-literature
Project description:BackgroundTo characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy.MethodsWe retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSCLC were found. Binary logistic regression and Cox regression were used to determine how EGFR ex20ins mutation subtypes and concomitant mutations are associated with PFS and OS.ResultsA total of 8,348 patients were screened and 101 advanced EGFR ex20ins NSCLC patients were detected. Fifty-five patients who received chemotherapy (n=49) or TKIs (n=6) as first-line treatment were recorded for PFS and OS. PFS and OS were significantly longer in the platinum-based chemotherapy group (median PFS: 7.6 versus 5.6 months; P=0.001; median OS: 19.9 versus 7.4 months; P=0.027) than in the TKI group. Common mutations include Ala767_Val769dupAlaSerVal (A767_V769dupASV), Ser768_Asp770dupSerValAsp (S768_D770dupSVD) and Ala763_Tyr764insPheGlnGluAla (A763_Y764insFQEA). On binary logistic regression, common mutations (OR =17.04, 95% CI: 1.39-209.56; P=0.027) and number of concomitant mutations ≤1 (OR =34.67, 95% CI: 2.02-595.48; P=0.015) is significantly associated with durable clinical benefit (DCB). On multivariable analysis, common mutations (HR =0.26, 95% CI: 0.0.10-0.63; P=0.003) and the number of concomitant mutations ≤1 (HR =0.33, 95% CI: 0.15-0.73; P=0.006) were significantly associated with longer PFS.ConclusionsCommon mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis.
| S-EPMC7661900 | biostudies-literature
Project description:BackgroundTo explore current status and choices regarding diagnosis and treatment of Parkinson's disease (PD) among physicians, general neurologists and movement disorders specialists in China via a national survey.MethodsThe cross-sectional questionnaire-based survey was conducted from November, 2010 to July, 2011. Six hundreds and twelve doctors from different cities in China were recruited for this study.Results68.6% (n=420) and 23.9% (n=146) of doctors have read the national and international guidelines, respectively. There was a larger proportion of movement disorders specialists reading the guidelines, in contrast to physicians and general neurologists (P<0.001). Up to 76.4% (n=465) and 81.8% (n=498) of doctors would choose standard oral levodopa test and conventional MRI(with T1 and T2), respectively; Whereas susceptibility weighed imaging(SWI)(16.1%; n=98), transcranial sonography (TCS) (1.8%; n=11) and functional neuroimaging test, such as single photon emission computed tomography(SPECT) (10.2%; n=62) and positron emission tomography(PET)(13.3%; n=81) were less used for suspected patients with PD in clinical practice. Doctors at different levels or from different hospitals and cities would choose different medication for motor complications and non-motor symptoms of patients with PD, in addition to initial drug selection for newly diagnosed PD. Doctors who had read the guidelines had significantly better knowledge of medication selections for PD under specific circumstances.ConclusionsCompared with commonly employed standard oral levodopa test and conventional MRI, SWI complements MRI, TCS and functional neuroimaging were less performed for diagnosis of PD in clinical practice in China. The choices of diagnostic methods and therapeutic strategy of PD vary among physicians, general neurologists and movement disorders specialists. Guideline awareness is markedly beneficial to reasonable PD medications strategy in China.
| S-EPMC3538053 | biostudies-literature
Project description:BackgroundGastrointestinal (GI) motility disorders are common in clinical settings, but physicians still lack sufficient understanding and effective management of these conditions.MethodsThis research assessed Egyptian physicians' knowledge, practices, and attitudes towards GI motility disorders. A cross-sectional survey employing a self-administered questionnaire was carried out among physicians in Egypt. The questionnaire addressed various aspects of physicians' understanding, practices, and attitudes regarding GI motility disorders. Data analysis was conducted using descriptive statistics and presented as frequencies and percentages.ResultsA total of 462 physicians took part in the study. Although nearly two-thirds of them knew about GI motility studies, a notable proportion lacked adequate knowledge about GI motility disorders. Notably, 84.2% correctly identified dysphagia as a critical symptom suggestive of an upper GI motility disorder. However, 13.4% incorrectly linked hematemesis with an upper GI motility disorder, and 16.7% expressed uncertainty. In terms of practice, around half of the participants encountered a small number of patients with GI motility disorders (less than 5 per week or even fewer). Only 29.7% felt confident in managing patients with motility disorders. Most participating physicians expressed a willingness to participate in training programs focused on motility disorders.ConclusionsThis study underscores a knowledge gap among Egyptian physicians concerning GI motility disorders. It suggests the necessity of tailored education and training programs to improve their competency and practice in this domain.
| S-EPMC11225201 | biostudies-literature
Project description:IntroductionThis retrospective study aimed to investigate treatment patterns and outcomes in patients with NSCLC harboring EGFR20ins in China. EGFR20ins mutations are associated with poor responses to EGFR-TKIs, and limited real-world data exist regarding the efficacy of various treatment modalities.MethodsIn this retrospective, single-center study, treatment outcomes, including PFS and ORR, were evaluated for different treatment regimens based on imaging assessments. The impact of mutation heterogeneity on treatment efficacy was also explored.ResultsData from 302 patients diagnosed with NSCLC with EGFR20ins were analyzed. EGFR-TKI monotherapy demonstrated suboptimal PFS compared to platinum-based chemotherapy in the first-line setting (3.00 m vs. 6.83 m, HR = 3.674, 95%CI = 2.48-5.44, p < 0.001). Platinum plus pemetrexed plus bevacizumab combination therapy showed improved PFS and ORR compared to platinum plus pemetrexed (7.50m vs. 5.43 m, HR = 0.593, 95%CI = 0.383-0.918, p = 0.019). In later-line treatments, monotherapy with EGFR-TKIs or ICIs exhibited suboptimal efficacy. The specific EGFR20ins subtype, A763_Y764insFQEA, showed favorable responses to EGFR-TKIs in real-world settings.ConclusionsThis large-scale real-world study provides valuable insights into the treatment patterns and outcomes of NSCLC patients with EGFR20ins mutations in China. These findings contribute to the understanding of EGFR20ins treatment and provide real-world benchmark for future clinical trials and drug development.
| S-EPMC11323489 | biostudies-literature
Project description: Not available
| S-EPMC9623475 | biostudies-literature
Project description:EGFR exon 20 insertion mutations (Ex20ins) and HER2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and HER2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.g. next-generation sequencing) that could allow the identification of these relatively rare molecular drivers. Second, highly active targeted drugs that might support a significant change in patients' prognosis when used as first-line therapy are required. In fact, although a few targeted drugs have so far demonstrated antitumour activity for these patients, mainly selective human epidermal receptor-tyrosine kinase inhibitors such as poziotinib and mobocertinib (for both molecular alterations), monoclonal antibodies such as amivantamab (for Ex20ins), and antibody-drug conjugates such as trastuzumab deruxtecan (for HER2 mutants), they are mostly confined for clinical use in pretreated patients. Finally, Ex20ins-targeted or HER2-targeted drugs might be difficult to access in different countries or regions worldwide. In the present review, we provide a concise but comprehensive summary of the challenges that lie ahead as we move towards personalized treatment of Ex20ins-mutant and HER2-mutant advanced NSCLC, also suggesting a treatment algorithm that could be followed for patients with these genetic aberrations.
| S-EPMC9354707 | biostudies-literature
Project description:IntroductionPatients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence.MethodsRWCP cohorts were derived from seven European and US real-world sources, comprising patients fulfilling CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared with a basket of RWCP treatments. Differences in prognostic characteristics were adjusted for using inverse probability weighting (IPW; average treatment effect among the treated [ATT]). Balance between cohorts was assessed using standardized mean differences (SMDs). Overall response rate (ORR; investigator- [INV] and independent review committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively.ResultsPre-adjustment, baseline characteristics were comparable between cohorts. IPW ATT-adjustment improved comparability, giving closely matched characteristics. ORR (INV) was 36.8% for amivantamab versus 17.0% for the adjusted EU + US cohort (response rate ratio [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52 months (hazard ratio [HR]: 0.47; p < 0.0001), 6.93 versus 4.17 months (HR: 0.55; p < 0.0001) and 12.42 versus 5.36 months (HR: 0.44; p < 0.0001) for amivantamab versus the adjusted EU + US cohort, respectively. Results were consistent versus EU- and US-only cohorts, and when using IRC assessment.ConclusionAdjusted comparisons demonstrated significantly improved outcomes for amivantamab versus RWCP, highlighting the value of amivantamab in addressing unmet need in patients with advanced EGFR Exon20ins NSCLC following platinum-based therapy.Trial registrationCHRYSALIS: NCT02609776.
| S-EPMC9988783 | biostudies-literature
Project description: Not available
| S-EPMC11632422 | biostudies-literature
Project description:Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR-mutant nonsmall cell lung cancers. We analysed real-world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify them. Three real-world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM. Mutation profiles consistent with in-frame EGFR ex20ins were summarized. GENIE, FoundationInsights, and GuardantINFORM datasets identified 180, 627, and 627 patients with EGFR ex20ins respectively. The most frequent insertion region of exon 20 was the near loop (~ 70%), followed by the far loop (~ 30%) and the helical (~ 3-6%) regions. GENIE, FoundationInsights, and GuardantINFORM datasets identified 41, 102, and 96 unique variants respectively. An analysis of variants projected that ~ 50% of EGFR ex20ins identified by NGS would have been missed by PCR-based assays. Given the breadth of EGFR ex20ins identified in the real-world US datasets, the ability of PCR to identify these mutations is limited. NGS platforms are more appropriate to identify patients likely to benefit from EGFR ex20ins-targeted therapies.
| S-EPMC9892822 | biostudies-literature