Update analysis of NEJ009: Gefitinib alone (G) versus gefitinib plus chemotherapy (GCP) for non-small cell lung cancer with mutated EGFR.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9081-9081
Author(s):  
Eisaku Miyauchi ◽  
Satoshi Morita ◽  
Atsushi Nakamura ◽  
Yukio Hosomi ◽  
Kana Watanabe ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Egfr Mutation ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Primary Endpoints ◽  
Efficacy Outcome ◽  
Significant Difference ◽  
Term Tolerability ◽  
Metastatic Sites ◽  
Clinical Trial Information

9081 Background: NEJ009 study is the first randomized phase III trial that compared gefitinib plus chemotherapy with gefitinib in patients with untreated NSCLC harboring EGFR mutations. We report an updated OS and long-term tolerability analysis, including subgroup analyses focusing on a type of EGFR mutation and metastatic sites. Methods: Patients were randomly assigned to gefitinib (gefitinib 250 mg PO, QD) and GCP regimen (gefitinib 250 mg PO, QD combined with carboplatin AUC 5 and pemetrexed 500 mg/m2 in a 3-week cycle for up to six cycles, followed by concurrent gefitinib and pemetrexed maintenance). This study tested multiple primary endpoints, PFS, PFS2, and OS, which were analyzed using a preplanned hierarchical sequential testing method. Results: Three hundred forty-five patients were randomly assigned (gefitinib, n = 172; GCP, n =170). At latest data cut-off (May 22, 2020), although there was no significant difference in OS between the groups (HR, 0.82; 95% CI, 0.64 to 1.06; P=0.13), GCP still demonstrated significantly better PFS and PFS2 compared to G. The updated median PFS, PFS2, and OS was 11.2 months, 18.0 months, and 38.5 months in the gefitinib group and 20.9 months, 20.9 months, and 49.0 months in the GCP group, respectively. No severe adverse events occurred in the period since the first report. Conclusions: This updated analysis confirmed that the GCP regimen achieved significantly better PFS and PFS2 with an acceptable safety profile compared with gefitinib alone. The efficacy outcome of GCP is more favorable than gefitinib monotherapy as first-line treatment of NSCLC with EGFR mutation. Clinical trial information: UMIN000006340. Clinical trial information: UMIN000006340. [Table: see text]

Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non–Small-Cell Lung Cancer in Asia (IPASS)

2011 ◽  
Vol 29 (21) ◽  
pp. 2866-2874 ◽  
Author(s):  
Masahiro Fukuoka ◽  
Yi-Long Wu ◽  
Sumitra Thongprasert ◽  
Patrapim Sunpaweravong ◽  
Swan-Swan Leong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Copy Number ◽  
Egfr Mutation ◽  
Gene Copy Number ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Gene Copy ◽  
First Line ◽  
Egfr Gene ◽  
Significant Difference

Purpose The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. Patients and Methods In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. Results OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation–positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation–negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation–positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). Conclusion EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation–positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.

scholarly journals Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in Mucinous Lung Cell Carcinomas

Folia Medica ◽  
2017 ◽  
Vol 59 (2) ◽  
pp. 174-182
Author(s):  
Sylvia N. Genova ◽  
Veselin T. Belovezhdov ◽  
Stoyan N. Bichev ◽  
Vladimir H. Danev
Keyword(s):  
Salivary Gland ◽  
Mutation Frequency ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Common Pattern ◽  
Specificity And Sensitivity ◽  
Napsin A ◽  
Significant Difference ◽  
Pcr Technology ◽  
Lung Adenocarcinomas

AbstractBackground:Invasive mucinous lung adenocarcinomas are rare and account for 2%–10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a weaker expression in mucinous adenocarcinomas compared with TTF1, but such correlation is still poorly researched.Aim:The aim of the study was to determine the frequency of mucinous to nonmucinous adenocarcinomas and compare specificity and sensitivity of monoclonal Napsin A with TTF1 in mucinous adenocarcinomas and define the frequency of EGFR mutations.Materials and methods:Eighty-four resected lung carcinomas were prospectively evaluated. All biopsies were analysed with p63, TTF1, monoclonal Napsin A, CK7, CK20 and CDX2 and were studied with real-time PCR technology.Results:In resected material we detected 49/84 (58.3%) adenocarcinomas and selected 21 mucinous adenocarcinomas out of 46 non-mucinous adenocarcinomas (45.6%). The most common pattern of mucinous adenocarcinomas is papillary - 24% and colloidal - 24%, followed by acinar - 19.2% and lepidic - 19.2%. mNapsin A was positive in 18/21 (85.7%) mucinous adenocarcinomas v/s 17/21 TTF1 positive (80.9%). EGFR mutations were detected in 3/21 cases with mucinous adenocarcinomas (14.3%): mucinous papillary, mucinous acinar and “salivary gland-like”.Conclusion:Our study demonstrates a high proportion of primary mucinous lung adenocarcinomas to primary non-mucinous adenocarcinomas. Sensitivity and specificity of mNapsin A and TTF1 did not show significant difference in pulmonary mucinous and non-mucinous adenocarcinomas, as mNapsin A gave greater sensitivity to mucinous adenocarcinomas. Our results indicate the same mutation frequency of EGFR in mucinous adenocarcinomas as mutation frequency detected in non-mucinous adenocarcinomas in the Bulgarian region.

Investigation of immune microenvironment in EGFR mutant NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20517-e20517
Author(s):  
Yi Hu ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Yuezong Bai ◽  
Fan Zhang
Keyword(s):  
T Cells ◽  
Egfr Mutation ◽  
Tumor Stroma ◽  
Median Number ◽  
Egfr Mutations ◽  
Wild Type ◽  
Immune Microenvironment ◽  
Regulatory Pathways ◽  
Significant Difference ◽  
Egfr Mutant

e20517 Background: Immune checkpoint inhibitor therapy has made great achievements in NSCLC, but patients with EGFR mutations have poor efficacy with immunotherapy. Previous studies have explored the expression of PD-L1, neo-antigen, co-mutation and regulatory pathways in EGFR mutate NSCLC. This work compared the immune microenvironment of EGFR mutant and wild-type NSCLC. Methods: Patients: NSCLC. Using multi-color immunohistochemistry (multi-IHC) to evaluate the expression of 2 indicators in tumors and tumor stroma, namely CD8+ T cell and macrophage. Shapiro-Wilk was used for normality test, and t-test or Mann-Whitney U test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 119 NSCLC patients, including 59 women (49.6%) and 60 men (50.4%), with a median age of 57. There were 68 patients (57.1%) with EGFR mutations, 19 patients (16%) with KRAS mutations, and 58 patients (48.7%) with TP53 mutations. multi-IHC results showed that, EGFR mutation Vs EGFR wild type samples, (1) the number and proportion of CD8+ T cells in tumor were not statistically different. The median number of CD8+ T cells in tumor stroma was 231.5 vs 359, p = 0.05 and the proportion of CD8+ T cells was 3.92% vs 5.64%, p = 0.02; (2) The median number of macrophage in tumors was 1522 vs 110, p < 0.01, and the proportion of macrophage cells was 24.93% Vs 1.38%, p < 0.01. The median value of macrophages in tumor stroma was 617.5 Vs 208, p < 0.01, and the proportion of macrophages cells was 10.88% vs 3.03%, p < 0.01. Conclusions: Compared with EGFR wild-type patients, EGFR mutation patients have a lower proportion of CD8+ T cells and a higher proportion of macrophages in the immune microenvironment.

Final overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7559-7559 ◽  
Author(s):  
Yan Sun ◽  
Yuankai Shi ◽  
Li Zhang ◽  
Xiaoqing Liu ◽  
Caicun Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Significant Difference ◽  
Biomarker Analysis ◽  
Nsclc Patients

7559 Background: A total of 399 pretreated patients with advanced NSCLC were randomly assigned to receive gefitinib or icotinib in the phase III ICOGEN trial, the first head-to-head phase III trial of EGFR-TKIs. The results of the primary endpoint, PFS, have been reported previously. This report represents the final OS and biomarker analysis results. Methods: EGFR mutation was evaluated by using Scorpion ARMS (QIAGEN, n=152). Overall survival was analyzed by Cox proportional-hazards model analysis at 82% maturity. Results: Median OS was 13.3 months for icotinib and 13.9 months for gefitinib (hazard ratio [HR] = 0.90; 95% CI, 0.79 to 1.02; P = .109). The EGFR mutation rate was 43% in the icotinib group and 59% in the gefitinib group. Compared to wild type patients, patients with EGFR mutation had longer PFS (median, 6.2m vs. 2.3m; P=.00001) as well as OS (median, 20.5m vs. 7.7m; P=.00001). There were no significant differences in PFS or OS between the two treatment groups in EGFR mutation-positive subgroup (median PFS, 7.8m vs. 5.3m for icotinib and gefitinib, respectively, P =.3162; median OS, 20.9m vs. 20.2m for icotinib and gefitinib, respectively, P =.7611.) or in EGFR mutation-negative subgroup (median PFS, 2.3m vs. 2.2m for icotinib and gefitinib, respectively, P =.1531; median OS, 7.8m vs. 6.9m for icotinib and gefitinib, respectively, P =.7885.). Conclusions: There is no statistically significant difference between icotinib and gefitinib in PFS or OS when given to NSCLC patients. This suggests that icotinib can provide similar OS benefits to gefitinib in advanced NSCLC patients. Moreover, EGFR mutation status is the strongest predictor in identifying which patients are most likely to benefit from icotinib.

ASPIRATION: Phase II study of continued erlotinib beyond RECIST progression in Asian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7614-TPS7614 ◽  
Author(s):  
Keunchil Park ◽  
Chun-Ming Tsai ◽  
Myung-ju Ahn ◽  
Chong-Jen Yu ◽  
Sang-We Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
Life Threatening ◽  
Pre Treatment

TPS7614 Background: First-line erlotinib (an EGFR tyrosine-kinase inhibitor) significantly increased progression-free survival (PFS) vs chemotherapy in phase III trials of pts with EGFR mutation-positive NSCLC. Discontinuation of erlotinib on RECIST disease progression (PD) may lead to rapid disease flare-up; continued erlotinib beyond RECIST PD may extend clinical benefit by slowing progression of this life-threatening disease. We describe ASPIRATION, a large, Asian, multicenter, single-arm, open-label, phase II trial (NCT01310036), which will increase understanding of first-line erlotinib and erlotinib continuation beyond RECIST PD in pts with EGFR-mutated NSCLC. Methods: Pts (n=204) ≥18 yrs with stage IV/recurrent NSCLC, ≥1 measurable lesion (≥10mm), ECOG performance status (PS) 0-2 and positive EGFR mutation status established by local pathology laboratory (that underwent voluntarily QA/QC) are eligible. All pts receive erlotinib 150mg/day. Tumor response is evaluated using RECIST (v1.1). The primary endpoint is PFS. At investigator's discretion, pts may continue on erlotinib beyond RECIST PD, e.g. if they have slow PD (>6 months of partial response/stable disease), asymptomatic minimal PD, or new brain metastasis controlled locally. Pts should not continue erlotinib if they have extracranial PD with symptoms; rapid PD and/or worsening of PS; or life-threatening complications. Pts continuing erlotinib who present with second RECIST PD will discontinue. Secondary endpoints include objective response rate, disease control rate, overall survival, and safety. For the exploratory biomarker study, pre-treatment tumor tissue blocks are collected; remaining tissue (after EGFR mutation testing for eligibility) will be analyzed centrally to study the association of biomarkers and clinical outcomes. Pre-treatment and post-treatment plasma and serum samples will be obtained at various time points for biomarker assays, including EGFR mutations and other candidate NSCLC biomarkers. Recruitment began in Apr 2011; the estimated final data collection for the primary endpoint is Dec 2014.

ACOSOG Z1041 (Alliance): Cardiac events (CE) among those receiving neoadjuvant anthracyclines (A) and taxanes with trastuzumab (T) for HER2+ breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
Michael Ewer ◽  
Vera J. Suman ◽  
Aman Buzdar ◽  
Linda Mackie McCall ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Ejection Fraction ◽  
Cardiac Risk ◽  
Operable Breast Cancer ◽  
Cardiac Events ◽  
Her2 Breast Cancer ◽  
A Value ◽  
Significant Difference ◽  
Clinical Trial Information

526 Background: Z1041 randomized women with HER2+ operable breast cancer to: FEC → P+T (Arm 1) or P+T → FEC+T (Arm 2). Treatment administered as 5-FU 500 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 day 1 of a 21-day cycle x 4; paclitaxel 80 mg/m2weekly x 12 and T 4 mg/kg once then 2 mg/kg weekly x 11. T was to continue q3 weeks post-op for 40 weeks. A secondary aim was to examine the cardiotoxicity (CE). Methods: Ejection fraction (EF) was measured at baseline (BL), between regimens (wk 12), prior to surgery (wk 24) and PRN. Eligibility: BL EF ≥ 55%. CEs included decline in EF of > 15%, or >10% points to a value < LLN. Reversibility was adjudicated by blinded investigators as reversible (R: recovery of EF to ≤ 5% below BL), partially reversible (PR: recovery of > 10% points from nadir, but ≤ 5% points below BL), indeterminate (IN: no additional EF data), or irreversible (IRR:follow-up EF studies showed no improvement). Results: Of the 280 patients (Arm 1: 138) who began treatment, 15 pts (Arm 1: 10; Arm 2: 5) did not receive T. The number of weeks of T was 13 (range: 1-18) in Arm 1 and 24 (range: 1-31) in Arm 2. Changes in EF and severe treatment related cardiac toxicities prior to surgery (sx) are tabled below. There were 271 pts (Arm 1: 131) who had post-BL EFs. Prior to sx, there were 11 CE (8.3%) in Arm 1 and 13 CE (9.2%) in Arm 2. CEs were R in 12 pts (Arm 1: 5; Arm 2: 7); PR in 6 pts (Arm 1: 4; Arm 2: 2); IN in 4 pts (Arm 1: 2; Arm 2: 3) and IRR in 1 Arm 2 pt. Conclusions: The number of CE events in arms 1 and 2 showed no significant difference; greater scatter was observed in arm 2 patients. While concern for late cardiac events makes ongoing cardiac surveillance prudent due to A, concomitant use of A and T appear to not be associated with increased cardiac risk. Clinical trial information: NCT00513292. [Table: see text]

10-yr follow-up results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
Thomas B. Julian ◽  
Stewart J. Anderson ◽  
David N. Krag ◽  
Seth P. Harlow ◽  
Joseph P. Costantino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Disease Free Survival ◽  
Outcome Data ◽  
Phase Iii ◽  
Absolute Difference ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
M Estimates

1000 Background: NSABP B-32, the largest surgical prospective randomized phase III trial was designed to compare overall survival (OS), disease-free survival (DFS), and morbidity between SNR alone vs SNR + AD in SN negative (-) pts. We present 10 yr outcome data for primary endpoints as well as updated data on the effect of occult metastases, found later in the SN by central, detailed pathologic analysis. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group [Grp] 1) or to SNR alone with AD only if SNs were positive (Grp2). 3,989 (71.1%) of 5,611 pts were SN-. 3,986 (99.9%) of these SN- pts had follow-up information: Grp 1: 1,975, Grp 2:2,011. Median time on study was 9.4 yrs. Cox proportional hazard models adjusting for study stratification variables were used to compare OS and DFS between the two groups. Two-sided p values were used. HR values > 1 indicate a more favorable outcome in Grp 1 Results: At 10 yrs, there continues to be no significant difference in OS between the two groups (HR: 1.11, p = 0.27). 10 yr Kaplan-Meier (K-M) estimates for OS are 87.8% for SNR alone and 88.9% for SNR + AD. There continues to be no significant difference in DFS between the two groups (HR: 1.01, p=0.92). 10-yr K-M estimates for DFS were 76.9% for both groups. Occult nodal disease was originally detected in 3,884 pts (15.8%) with SN- on initial H and E analysis. Comparisons between the groups with and without occult disease yielded an adjusted HR for OS: 1.25 (p = 0.08) with an absolute difference at 10 yrs of 2.8% and a HR for DFS: 1.24 (p = 0.018) with an absolute difference of 4.1%. The cumulative incidences of local-regional events were low (10-yr values: SNR 4.0%, SNR+AD, 4.3%) and not significant (HR: 0.95, p = 0.77). Conclusions: At 10 yrs there continues to be no significant differences in OS and DFS between SNR and SNR + AD in pts with negative SN. The relative increase in risk of DFS and OS for pts with occult SN metastases remains stable. Support: PHS grants: NSABP: U10CA-12027, U10CA-37377, U10CA-69651, U10CA-69974; VT Ca Cntr: P30 CA22435; DNK: 5RO1CA074137 NCI Dpt HHS. Clinical trial information: NCT00003830.

Interim results of a randomized phase II study of PEGPH20 added to nab-paclitaxel/gemcitabine in patients with stage IV previously untreated pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Sunil R. Hingorani ◽  
William Proctor Harris ◽  
Tara Elisabeth Seery ◽  
Lei Zheng ◽  
Darren Sigal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Randomized Study ◽  
Safety Data ◽  
Stage Iv ◽  
Phase Iii ◽  
Clinical Hold ◽  
Stage 1 ◽  
Clinical Trial Information

439 Background: Poor outcome in pancreatic cancer (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20, PEGylated recombinant human hyaluronidase, potentiates chemotherapy by depleting HA in tumors. Methods: In an ongoing, phase II, open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gemcitabine (Gem) (PAG) vs Nab+Gem (AG) in previously untreated stage IV PDA, pts receive PEGPH20 3 µg/kg twice weekly (C1), then weekly (C2+) with standard AG dosing. HA status was tested retrospectively. After a temporary clinical hold (Apr-Jul 2014) for an imbalance in thromboembolic (TE) events (29% PAG vs 15% AG), the protocol was amended to exclude high-TE-risk pts and add enoxaparin (LMWH) prophylaxis. Endpoints are PFS and TE events (primary); PFS and ORR by HA level and OS (secondary). Efficacy and safety data through Dec 2014 are for pts enrolled up to clinical hold (Stage 1); TE data are through Sep 2015 (Stage 2). Results: 135 pts were treated (74 PAG, 61 AG). PFS results are shown below (median follow-up 7 mo). In HA-high pts receiving PAG vs AG, ORR was 52% (1 CR) vs 24% (P=.038); ORR was 37% vs 38% in HA-low pts. OS was 12 mo vs 9 mo (HR=0.62) despite 12/23 PAG pts discontinuing PEGPH20 at clinical hold. Common ADRs (PAG vs AG) included peripheral edema (58% vs 31%), muscle spasms (55% vs 1.6%), and neutropenia (32% vs 18%). TE events were: Stage 1 42% vs 25% (no LMWH); Stage 2 (with LMWH; 40 mg/d or 40 mg/d increased to 1 mg/kg/d) 28% vs 29%; (1 mg/kg/d) 5% vs 6%; overall (40 mg/d or 1 mg/kg/d) 13% each arm (to be updated). Conclusions: Pts with HA-high tumors receiving PAG, vs AG, showed significant improvements in PFS and ORR and a trend toward improved OS. PAG was well tolerated, with TE events reduced with LMWH prophylaxis. A global phase III trial of PAG will initiate Q1 2016. Clinical Trial Information: NCT01839487. Clinical trial information: NCT01839487. [Table: see text]

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