The different efficacy of gefitinib or erlotinib according to epidermal growth factor receptor exon 19 and exon 21 mutations in Korean non-small cell lung cancer patients

Background  

Epidermal growth factor receptor (EGFR) mutations are associated with sensitivity to gefitinib or erlotinib in non-small cell lung cancer (NSCLC). We investigated the relationships between the two most common types of somatic EGFR mutations, exon 19 deletions and L858R mutations, and clinical outcomes of Korean NSCLC patients after treatment with gefitinib or erlotinib.     

Uncommon EGFR mutations in lung carcinoma: features and treatment outcomes in a retrospective French cohort

BackgroundThe best management for rare epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung carcinoma (NSCLC) remains uncertain. The literature indicates that response to usual treatment could differ in certain subgroups such as exon 20 insertion/duplication (E20ID), other single uncommon mutation (OSUM), and EGFR complex mutation (ECM).MethodsIn this observational, regional, multi-center, retrospective study, we gathered data on uncommon EGFR mutations in NSCLC from 2007 to 2021. We analyzed patient characteristics, prognostic factors and treatment outcomes [objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS)].ResultsAmong 119 patients with an uncommon EGFR mutant, 34 harbored E20ID, 23 ECM, and 62 OSUM. There were significantly more non-smokers in E20ID. Female gender and performance status <2 were associated with a better prognosis. Among the 97 metastatic patients with available data for 1st line treatment, median estimated OS was 21 months (95% CI: 18–31 months), with better non-significant OS for ECM. Median estimated PFS was 7 months (95% CI: 4–9 months). We found significant differences in ORR, DCR and PFS favoring 1st line chemotherapy for E20ID, whereas the outcomes for OSUM and ECM were more favorable for tyrosine kinase inhibitor (TKI) (mainly 2nd and 3rd generation).ConclusionsThere were variations in treatment outcomes among subgroups in our cohort. Exon 20 insertions showed better ORR and PFS with 1st line chemotherapy compared to TKI. Conversely, other rare EGFR mutations including ECM had better ORR and PFS with TKI than chemotherapy. There was no significant difference in OS among treatment groups overall or within rare mutation subgroups.     

Prediction of epidermal growth factor receptor mutations in the plasma/pleural effusion to efficacy of gefitinib treatment in advanced non-small cell lung cancer

Purpose  

Recently, mutations in the epidermal growth factor receptor (EGFR) gene were reported to correlate with EGFR tyrosine kinase inhibitor response in advanced non-small cell lung cancer (NSCLC). In this study, we attempted to detect EGFR mutations in plasma and pleural effusion samples and to make clear its correlations with gefitinib response and survival in NSCLC patients.     

BRCA1表达与吉非替尼治疗EGFR基因突变型晚期非小细胞肺癌疗效的关系

目的：探讨BRCA1表达与吉非替尼治疗EGFR突变型晚期非小细胞肺癌患者的疗效关系。方法：纳入我院2013年1月至2014年11月确诊为EGFR突变型晚期非小细胞肺癌的患者50例,口服吉非替尼进行治疗,直至疾病进展或者出现不可耐受的毒副反应,采用免疫组织化学方法检测EGFR突变型晚期非小细胞肺癌患者中BRCA1的表达情况,并通过收集的临床资料回顾性分析吉非替尼对EGFR突变型晚期非小细胞肺癌病人的治疗效果。结果：BRCA1高表达率为36.00%(18/50),BRCA1高表达组吉非替尼有效率为33.33%(6/18),BRCA1低表达组吉非替尼有效率为68.75%(22/32),两者差异有统计学意义(P＜0.05)。结论：吉非替尼治疗EGFR突变型晚期非小细胞肺癌患者中,BRCA1低表达患者受益比高表达患者明显,BRCA1可以作为吉非替尼治疗EGFR突变型晚期非小细胞肺癌的预测因素。     

KRAS和表皮生长因子受体突变基因与原发性非小细胞肺癌的相关性

目的 研究KRAS和表皮生长因子受体(EGFR)基因在原发性非小细胞肺癌(NSCLC)中的突变状态以及其与靶向治疗效果的相关性。方法 收集郑州大学第一附属医院收治的150例经病理证实的NSCLC患者原发肿瘤及受累的淋巴结标本,进行KRAS和EGFR突变基因序列分析。150例中12例患者纵隔淋巴结转移灶经DNA序列分析发现EGFR基因突变后给予吉非替尼进行术前辅助治疗。结果150对（分别为原发灶和受累淋巴结）标本中,2例原发肿瘤和10例淋巴结转移灶中检测到KRAS突变基因,35例原发肿瘤和44例淋巴结转移灶中检测到EGFR突变基因。KRAS和EGFR基因在原发灶和转移灶中不一致的比率分别为6.7％ (10/150)和8.7％ (13/150)。1例原发肿瘤无EGFR突变的患者接受吉非替尼治疗后效果不佳。结论 NSCLC患者原发灶和转移灶中KRAS和EGFR基因突变状态不一致,这对于应用酪氨酸激酶抑制剂靶向治疗NSCLC具有重要的参考意义。     

Gefitinib therapy in patients with advanced non-small cell lung cancer with or without testing for epidermal growth factor receptor (EGFR) mutations

Gefitinib is effective in treating advanced non-small cell lung cancer (NSCLC), especially in Asian patients in whom the prevalence of epidermal growth factor receptor (EGFR) mutation was high. We analyzed our gefitinib treatment use in patients for advanced NSCLC to study the influence of clinical factors on the treatment outcomes in a tertiary referral medical center in Taiwan. Clinical data and EGFR mutational status of the tumors were collected. A total of 907 patients received gefitinib for advanced NSCLC: 466 patients (51.4%) underwent testing for EGFR mutations, and the other 441 patients did not. In the 466 patients who were tested for EGFR mutations, 272 (58.4%) had EGFR mutations, and an EGFR mutation was a prominent factor for objective response to gefitinib (67.3% vs. 18.3% in wildtype EGFR, p < 0.001). In the 441 patients who did not receive EGFR mutation sequencing, nonsmoker status, female sex, and adenocarcinoma cell type were predictors for better gefitinib response (p < 0.005). We found that testing for EGFR mutations was helpful in NSCLC patients in Taiwan to guide the use of gefitinib. In patients with positive activating EGFR mutations, gefitinib efficacy was prominent and significant. Therefore, analysis for EGFR mutation should be advocated. In those patients who have unknown EGFR mutation status, demographic and histopathology characteristics can be relied on to judge the potential efficacy of gefitinib use.     

Erlotinib as a salvage treatment after gefitinib failure for advanced non-small-cell lung cancer patients with brain metastasis: A successful case report and review

Rationale:The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.Patient concerns:We described a 55-year-old man with good performance status (PS).Diagnoses:He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018.Interventions:He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib.Outcomes:It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable.Lessions:This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.     

Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy

Purpose  Two large, randomized, placebo-controlled trials (IRESSA NSCLC Trial Assessing Combination Therapy; INTACT 1 and 2) in non-small-cell lung cancer (NSCLC) failed to show survival benefit for gefitinib (IRESSA) in combination with first-line platinum-based chemotherapy. Epidermal growth factor receptor (EGFR) staining was assessed retrospectively in relation to survival response to gefitinib in combination with chemotherapy. Methods  Tumor biopsies obtained prior to start of therapy were assessed by immunohistochemistry for EGFR using the Dako EGFR pharmDx assay™ (Dako, Denmark). Analyses were stratified by trial and performed independently for patients randomized to placebo and gefitinib as well as for both treatment groups combined. A restricted backwards elimination Cox regression analysis was conducted to identify independent EGFR factors that were statistically significant (P < 0.10), and these were also tested for treatment interaction to assess if they served as predictive factors. Results  Analyses found two statistically significant EGFR-based prognostic factors representing growth pattern and percent membrane staining in patients treated with gefitinib (P = 0.0023), placebo (P = 0.0128), and both combined (P < 0.0001). The prognostic effect was independent of other known prognostic factors. There was no predictive effect of either the growth pattern or membrane staining variable. Conclusions  While some previous studies indicate that higher EGFR expression correlates with poor survival, our analyses provide statistically significant evidence that the combination of EGFR expression and growth pattern is a strong prognostic indicator for improved survival within this setting. The effects of membrane staining and growth pattern are still significant when adjusting for mutation. IRESSA is a trademark of the AstraZeneca group of companies. PharmDx assay is a trademark of Dako.     

Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling

Purpose  The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) has been linked to activating mutations in the EGFR gene. So far these mutations have been extensively characterized in established cell lines. The aim of this study was to determine the effects of EGFR mutations on downstream signaling in human tumor specimens. Methods  We have looked for mutations of the EGFR gene in specimens of 67 patients with NSCLC and correlated these with EGFR phosphorylation and the activity of its three main downstream signaling cascades Akt, MAPK and Stat3 by immunohistochemistry. Results  We show that the phosphorylation of tyrosine residues 922 and 1173, but not 1068, are primarily affected by the activating EGFR mutations. Akt activity was significantly higher in patients with EGFR mutations but we found no difference in Stat3 or MAPK phosphorylation. Our results suggest that EGFR mutations not only increase receptor activity, but also alter responses of downstream signaling cascades in human NSCLCs and that these finding differ from results obtained in cell lines. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A Retrospective Comparison of Trastuzumab Plus Cisplatin and Trastuzumab Plus Capecitabine in Elderly HER2-Positive Advanced Gastric Cancer Patients

A combination of trastuzumab and cisplatin or trastuzumab and capecitabine has been confirmed to be effective for treating adverse effects in with HER2-positive advanced gastric cancer (AGC) patients. We retrospectively compared the activity and safety of trastuzumab plus cisplatin (HP) and trastuzumab plus capecitabine (HX) for elderly HER2-positive AGC patients.Ninety two HER2-positive AGC patients were included in this study; of those 48 patients received trastuzumab (course 1, 8 mg/kg followed by course 2, onward, 6 mg/kg on day 1) plus cisplatin (60 mg/m²) intravenously on day 1 of a 3-week cycle and 44 patients received trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg/kg) plus intravenous oral capecitabine (1000 mg/m² twice daily on days 1–14), every 3 weeks. The primary end point was overall survival (OS). The secondary end points included objective response rate (ORR), progression-free survival (PFS), and toxicity.The median age was 71 years in both groups. The median OS was 15.5 months in the HP group and 17.0 months in the HX group, with no significant difference between the 2 groups (P = 0.78). There were also no significant differences in PFS (median 6.6 months vs 7.2 months, respectively; P = 0.90) and ORR (58.3% vs 59.1%, respectively; P = 1.00) between the HP group and the HX group. The major grade 3 or 4 adverse events in the HP group and the HX group were neutropenia (35.4% vs 29.5%, respectively), followed by anorexia (25.0% vs 22.7%, respectively), and anemia (16.7% vs 13.6%, respectively), no significant differences were observed.HP and HX were associated with similar efficacy and safety in HER2-positive AGC patients.     

Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer

The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.     

ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines

Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). The differences in intracellular signaling networks between gefitinib-sensitive and -resistant NSCLCs remain poorly understood. In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. To elucidate the mechanism underlying this observation, we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to activate the PI3K/Akt pathway. In fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs.     

Meta-analysis of phase III trials of docetaxel alone or in combination with chemotherapy in metastatic breast cancer

Purpose  

Whether combination chemotherapy offers an advantage over sequential therapy in metastatic breast cancer (MBC) is still an unsettled issue. Polychemotherapy regimens containing taxanes has been shown to increase overall survival (OS), time to tumor progression (TTP), and overall response rate (ORR) when compared with regimens that did not contain a taxanes, while taxane-based doublets have a statistically significant benefit over single-agent taxane only for progression-free survival. However, the term “taxanes” generally includes both paclitaxel and docetaxel, drugs with different clinical activity. Aim of this work is to compare OS, TTP, and ORR in patients with MBC receiving docetaxel alone or in combination with chemotherapy using a formal meta-analysis.     

Efficacy and safety profile of combining agents against epidermal growth factor receptor or vascular endothelium growth factor receptor with gemcitabine-based chemotherapy in patients with advanced pancreatic cancer: A meta-analysis

ObjectivesSeveral clinical trials have been published on gemcitabine-based chemotherapy with or without addition of agents against epidermal growth factor receptor (EGFR) or vascular endothelium growth factor receptor (VEGFR) in patients with advanced pancreatic cancer, however, with diverse results. The objective of this study was to perform a meta-analysis of the published trials.MethodsThe database of CENTRAL, MEDLINE and EMBASE were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated the efficacy and safety profile of adding targeted agents against EGFR or VEGFR to gemcitabine-based chemotherapy in patients with advanced pancreatic cancer. The primary outcome was overall survival (OS) while secondary outcomes included progression free survival (PFS) and overall response rate (ORR). Toxicity profiles were also assessed. Review Manager 5.1 was used to perform the analysis.ResultsResults reported from 6 RCTs involving 2733 patients were included in the analysis. Compared to gemcitabine-based chemotherapy alone, addition of an agent against EGFR resulted in significant longer OS [Hazard ratios (HR) 0.89 (0.79–0.99), p = 0.04] and longer PFS [HR 0.87 (0.79–0.97), p = 0.01], but no significant difference in ORR [RR 1.18 (0.82–1.70), p = 0.36]. The addition of an agent against VEGFR resulted in higher ORR [RR 1.54 (1.03–2.30), p = 0.04], but no advantage in OS [HR 0.95 (0.83–1.09), p = 0.47] or PFS [HR 0.97 (0.77–1.23), p = 0.82].ConclusionsAddition of an agent against EGFR to gemcitabine-based chemotherapy improved OS compared to gemcitabine-based chemotherapy alone in patients with advanced pancreatic cancer, while addition of an agent against VEGFR showed a modest improvement in ORR but not PFS and OS.     

Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer

To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P = 0.0023). Smoking status (never smoker vs. smoker, P = 0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P = 0.0011), but not EGFR amplification (P = 0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P = 0.0125), but not correlated with prognosis (P = 0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.     

The Efficacy of Erlotinib Versus Conventional Chemotherapy for Advanced Nonsmall-Cell Lung Cancer: A PRISMA-Compliant Systematic Review With Meta-Regression and Meta-Analysis

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths. Erlotinib is the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations.We conducted a meta-analysis to compare the efficacy of erlotinib and chemotherapy for advanced NSCLC, and evaluated the efficacy of them to provide references for further clinical practice and research.PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, and Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. HR with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS), relative risk (RR) with 95% CIs for objective response rate (ORR) and 1-year survival rate (OSR) were all extracted. If the I² was ≤40%, then the trial was considered to be heterogeneous, and a fixed-effects model was selected. Otherwise, a random-effects model was used. Meta-regression and sensitivity analyses were conducted to determine the possible heterogeneity causes and to further identify the influence of the various exclusion criteria on the overall risk estimate.The pooled analysis demonstrated a PFS HR of 0.93 (95% CI = 0.73, 1.19) for erlotinib versus chemotherapy and an ORR of 18.43% versus 22.07%, respectively. The OS HR was 1.02 (95%CI = 0.93, 1.12). The HRs for PFS estimated based on 10 trials involving 1101 patients were 0.22 (95% CI = 0.15, 0.29) and 1.27 (95% CI = 1.04, 1.48) in EGFR mutation-type and wild-type patients, respectively. The HRs for OS calculated from 4 studies including 681 participants were 0.83 (95% CI = 0.61, 1.05) and 0.86 (95% CI = 0.68, 1.04) in EGFR mutation-type and wild-type patients, respectively. The 1-year survival rates were 31.31% and 32.41%, respectively.Overall, the present meta-analysis suggested that erlotinib did not improve the ORR, PFS, OS or the 1-year survival rate for whole patients. However, erlotinib could benefit patients with EGFR mutation in terms of PFS, but the OS does not benefit from it for these patients. Further studies of erlotinib for these subgroup patients are warranted.     

Clinical outcomes of advanced non-small cell lung cancer patients screened for epidermal growth factor receptor gene mutations

Purpose  

To evaluate the relationship between the epidermal growth factor receptor (EGFR) mutation status and the effectiveness of gefitinib monotherapy or chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).     

非小细胞肺癌患者EGFR、ALK基因突变及临床病理特征与预后的相关性研究

目的探讨非小细胞肺癌(NSCLC)患者EGFR、ALK基因突变状态及病理特征,分析二者与患者预后情况相关性。方法收集2015年1月至2018年1月苏州大学附属第一医院病理确诊的NSCLC病例262例,记录患者临床病理特征及转归,采用突变增阻滞系统(ARMS)-Taqman探针法及RT-PCR检测患者肿瘤样本的EGFR和ALK基因外显子突变情况,采用Kaplan-Meier法和Cox风险回归考察不同基因突变情况的预后、临床病理特征与临床结局的相关性。结果262例NSCLC患者中,168例为野生型,ALK突变12例,突变率4.6%;EGFR突变82例,突变率31.30%,其中18号外显子突变2例,19号外显子突变37例,20号外显子突变9例,21号外显子突变31例;各组间年龄、病理类型比较差异有统计学意义,P<0.05;Wild type组中位OS时间11.6月,ALK组中位OS时间15.0月,EGFR组中位OS时间36.8月,EGFR组OS明显优于ALK组OS时间及Wild type组OS时间,P<0.05;EGFR19号外显子突变组、21号外显子突变组OS生存时间显著高于18号外显子突变组和20号外显子突变组,P<0.05;EGFR阴性(RR=15.751,95%CI:9.252~26.816)、鳞癌(RR=18.344,95%CI:6.187~54.388)为OS的危险因素。结论EGFR突变状态、病理类型对非小细胞肺癌预后具有良好的预测价值,鳞癌和EGFR阴性患者生存期短。EGFR基因少见突变(18号外显子、20号外显子)患者的中位OS时间更短。     

Characterization of PI3KCA and BRAF mutations in gastric adenocarcinoma: An approach to a personalized targeted therapy for Moroccan HER2 overexpressed patients

Background and study aims

Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of PI3KCA and BRAF mutations in Moroccan HER2 overexpressed patients, in order to introduce targeted therapy in the arsenal of therapeutic modalities for management in Morocco.

Dramatic response to osimertinib combined with crizotinib in EGFR T790 M mutation only in blood and Met amplification only in tumor tissue expressive non-small cell lung cancer: A case report

Rationale:Besides the T790 M mutation, it may coexist with bypass pathway activation in real clinical cases for patients with EGFR mutations who resisted to the first- and second-generation tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). There are limited clinical trial data describing the efficacy of osimertinib combined with MET inhibition in EGFR T790M-mutant NSCLC patients with Met amplification.Patient concerns:A non-smoking 53-year-old male patient with lung adenocarcinoma underwent gefitinib, afatinib, and osimertinib combined with crizotinib treatment and developed different EGFR resistance mutations.Diagnoses:The patient was diagnosed with lung adenocarcinoma (stage cT4N2M0, IIIB). After resistance to the therapy targeting EGFR exon 21 L858R point mutation, T790 M mutation was detected in liquid biopsy and Met amplification was detected via tissue biopsy by next-generation sequencing (NGS).Interventions:The patient received systemic treatments, including chemotherapy, gefitinib, afatinib, and osimertinib combined with crizotinib.Outcomes:The patient died of multisystem organ failure and had an overall survival of 24 months.Lessons:Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.