A survey on Japanese thoracic oncologists’ preference on treatment strategy for EGFR-mutant or EML4-ALK-mutant non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19124-e19124
Author(s):  
Katsuyuki Hotta ◽  
Katsuyuki Kiura ◽  
Masarhiro Tabata ◽  
Nagio Takigawa ◽  
Mitsune Tanimoto ◽  
...  
Keyword(s):  
Survival Data ◽  
Good Condition ◽  
Genetic Alterations ◽  
First Line ◽  
Alk Rearrangement ◽  
Platinum Based Chemotherapy ◽  
Alk Positive ◽  
Gene Status ◽  
Egfr Mutant ◽  
Line Setting

e19124 Background: NSCLC pts have become categorized based on two genetic alterations in their tumors, EGFR and EML4-ALK, to provide personalized therapy. In EGFR-mutant NSCLC, EGFR-TKI yields a comparable survival with platinum-based chemotherapy, suggesting either of them can be initiated first, and its choice seems to depend partly on oncologists’ preference. As for the other, EML4-ALK, NCCN guideline recommends first-line crizotinib use despite no relevant survival data. The decision whether to choose crizotinib might be also influenced by oncologists’ preference. We here assessed their preference. Methods: The Japanese thoracic oncologists were asked to complete a self-administered questionnaire at the Japanese meeting specific for thoracic oncology. Results: Of 3,046 subjects, 871 (29%) responded voluntarily to a survey, mainly consisting of medical and surgical oncologists (93%). Majority considered EGFR mutation status should be checked at the time of diagnosis (89%), whereas only 60% and 33% reported EML4-ALK gene status would be assessed at the time of diagnosis and until the initiation of second-line setting, respectively. The subjects also considered pts with EGFR-wild-typed tumor and pts with clinical characteristics possibly related to EML4-ALK rearrangement should selectively receive EML4-ALK gene status check rather than all NSCLC pts (57%, 22% and 16%, respectively). Among the subjects, 52% preferred to choose gefitinib rather than platinum in the first-line setting in EGFR-mutant NSCLC, whilst 44% preferred crizotinib to platinum in the first-line setting in EML4-ALK-positive NSCLC. The major reasons why they chose gefitinib in EGFR-mutant NSCLC were ‘PFS is better’ (36%) and ‘it is easy to improve QOL’ (25%), whereas ‘PFS is better’ (43%), and ‘I want to prescribe when patients are still in good condition’ (19%) were the predominant reasons for choosing crizotinib in EML4-ALK-positive NSCLC. Conclusions: About half of the subjects preferred each molecular-targeted agent to the conventional cytotoxic chemotherapy in first-line setting. They considered better PFS was important in the treatment of EGFR-mutant or EML4-ALK-mutant NSCLC.

scholarly journals Emerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer

2013 ◽  
Vol 31 (31) ◽  
pp. 3987-3996 ◽  
Author(s):  
Justin F. Gainor ◽  
Alice T. Shaw
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Genetic Alterations ◽  
Anaplastic Lymphoma ◽  
Development Of Resistance ◽  
Tki Resistance ◽  
Alk Positive ◽  
Egfr Mutant

The success of tyrosine kinase inhibitors (TKIs) in select patients with non–small-cell lung cancer (NSCLC) has transformed management of the disease, placing new emphasis on understanding the molecular characteristics of tumor specimens. It is now recognized that genetic alterations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes of NSCLC that are highly responsive to genotype-directed TKIs. Despite this initial sensitivity, however, the long-term effectiveness of such therapies is universally limited by the development of resistance. Identifying the mechanisms underlying this resistance is an area of intense, ongoing investigation. In this review, we provide an overview of recent experience in the field, focusing on results from preclinical resistance models and studies of patient-derived, TKI-resistant tumor specimens. Although diverse TKI resistance mechanisms have been identified within EGFR-mutant and ALK-positive patients, we highlight common principles of resistance shared between these groups. These include the development of secondary mutations in the kinase target, gene amplification of the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant and ALK-positive patients alike, acquired resistance may also be a dynamic and multifactorial process that may necessitate the use of treatment combinations. We believe that insights into the mechanisms of TKI resistance in patients with EGFR mutations or ALK rearrangements may inform the development of novel treatment strategies in NSCLC, which may also be generalizable to other kinase-driven malignancies.

scholarly journals Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma

2019 ◽  
Vol 30 ◽  
pp. ix164 ◽  
Author(s):  
C.S. Chai ◽  
C.K. Liam ◽  
O. Po Lin ◽  
Y.K. Pang ◽  
G.F. Ho ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
First Line ◽  
Egfr Mutant ◽  
Line Setting

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 415-415
Author(s):  
Husam Alqaisi ◽  
Zachary William Neil Veitch ◽  
Carlos Stecca ◽  
Jeenan Kaiser ◽  
Scott A. North ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
First Line ◽  
Ecog Performance Status ◽  
Cancer Centre ◽  
Platinum Based Chemotherapy ◽  
Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

Chemosensitivity and clinical features of EML4-ALK-positive patients with advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18145-e18145 ◽  
Author(s):  
Jangchul Park ◽  
Chiaki Kondo ◽  
Junichi Shimizu ◽  
Yoshitsugu Horio ◽  
Kimihide Yoshida ◽  
...  
Keyword(s):  
Stage Iv ◽  
Cytotoxic Agents ◽  
Advanced Stage ◽  
Second Line ◽  
First Line ◽  
Treatment Regimens ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Alk Positive ◽  
Line Setting

e18145 Background: Lung cancers that harbor EML4-ALK can be effectively treated with anaplastic lymphoma kinase (ALK) inhibitors. Recent reports showed that pemetrexed-based therapy might be an effective treatment in patients with ALK-positive NSCLC. However, the efficacy of other regimens is still not known. The purpose of this study is to investigate the clinical characteristics, the efficacy of the cytotoxic chemotherapy in the first and second line setting in EML4-ALK positive NSCLC with advanced stage. Methods: EML4-ALK fusion was screened with RT-PCR and immunohistochemistry. When positive results were obtained with either method, gene rearrangement of ALK was confirmed with fluorescent in-situ hybridization. The clinical efficacy of chemotherapy was evaluated retrospectively. Results: We evaluated 20 EML4-ALK positive patients with advanced stage. Twelve patients were without a history of smoking, and 6 light smokers and 2 smokers. Seventeen (85%) of 20 had stage IV disease. Nine cases were male, and 11 were female. The mean age was 46.3 years (range, 26-79 years). Most of the CT findings at the primary site were masses or nodules, while two cases showed air-space consolidation. In the first line chemotherapy, most of the treatment regimens included carboplatin or cisplatin in combination with one or more therapeutic agents, such as taxans, bevacizumab except one case who was treated only by S-1. In 13 cases which were evaluable, 7/13 (53.8%) had a PR, 4/13 (30.8%) had SD, and 2/13 (15.4%) had PD. The treatment regimens in the second line setting included one therapeutic agent such as docetaxel, pemetrexed, S-1 or an oral ALK inhibitor. Among 10 evaluable cases in the second line setting, 2/10 (20%) had a PR, 5/10 (50%) had SD, and 3/10 (30%) had PD. Two patients who had a PR were all treated by oral ALK inhibitor. Within 7 patients who were treated by cytotoxic agents, none had clinical response. Conclusions: Our study suggests that EML4-ALK positive patients may show relatively favorable response to cytotoxic drug in the first line setting, but low response in the second line setting. These data might be helpful for further clinical trials including EML4-ALK positive patients.

Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20565-e20565 ◽  
Author(s):  
Ruben Salanova ◽  
Julio C Calderazzo Pereyra ◽  
Laura Leguina ◽  
Asuncion Bena ◽  
Mariana Barberis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Mutational Status ◽  
Alk Positive ◽  
Egfr Mutant ◽  
Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

scholarly journals Efficacy Differences of First-line EGFR-TKIs Alone vs. in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alteration(s)

2021 ◽  
Author(s):  
Guowei Zhang ◽  
Ruirui Cheng ◽  
Yuanyuan Niu ◽  
Huijuan Wang ◽  
Xiangtao Yan ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Egfr Mutation ◽  
Objective Response ◽  
Genetic Alterations ◽  
Monotherapy Group ◽  
First Line ◽  
Egfr Tki

Abstract Objective: To explore whether EGFR-TKI combined with chemotherapy would benefit patients with advanced lung adenocarcinoma with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. Materials and Methods: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKI and chemotherapy combination or EGFR-TKI monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. Results: 107 patients were included, including 63 in the combination therapy group and 44 in the monotherapy group. The ORR were 78% and 50% (P =0.003), and DCR were 97% and 77% (P =0.002), respectively. At a median follow-up of 13.7 months, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 and 5.3 months, respectively (P <0.0001). Median OS was unreached in the combination group, and 27.8 months in the monotherapy group (P =0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS. Conclusion: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKI and chemotherapy was significantly superior to EGFR-TKI monotherapy, which should be the preferred treatment option.

Preliminary results from a phase II study of celecoxib plus chemotherapy in patients with untreated advanced NSCLC

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18188-18188
Author(s):  
J. Wang ◽  
X. Liu ◽  
L. Yang ◽  
Q. Guo ◽  
L. Yang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Advanced Nsclc ◽  
Patient Death ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Cox 2 ◽  
Grade 3

18188 Background: Preclinical studies indicated that cyclooxygenase-2(cox-2) inhibitor celecoxib may enhance antitumor efficacy of cytotoxics, and combination with chemotherapy had acceptable tolerability in a phase I trial. This phase II trial evaluated the efficacy and safety of the celecoxib plus platinum-based chemotherapy in advanced NSCLC as first-line chemotherapy. Methods: Patients: chemotherapy naïve, IIIB (w/malignant effusion) IV, PS 0–2; treated with platinum-based chemotherapy (Gemcitabine 1,200 mg/m2 d1, 2, Cisplatin 75 mg/m2 d1 Q3w or Docetaxel 35 mg/m2 d1,8,15, cisplatin 75 mg/m2 d1, Q4w), and plus celecoxib 400 mg p.o. bid., until evidence of disease progression or toxicity. Primary endpoint: median survival; secondary endpoints: response rate and toxicity. Results: From 3/05 to 6/06, 30 pts with cox-2 positive expression detected by ICH were treated; 27 evaluable for response and toxicity; M/F: 18/12; median age 64 (42–74); PS 0/1/2: 3/23/4; Path: adeno/squamous: 60%/40%; StageIII/IV: 35%/65%. Toxicity: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 40% (11/27) and 30%(8/27) patients, respectively. One patient death was considered possible treatment related. Response: CR:0; PR: 14 (52%; 95% CI 32%-76%); SD: 6 (22%; 95% CI 14%-32%); PD:7 (26%; 95% CI 19%-36%). Median duration of response and stable disease: 6.4 (range 3.5–7.5) and 3.5 months (range 1.5–8.0), respectively. Survival is too early to evaluate. Conclusions: Celecoxib in combination with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients with previously untreated advanced NSCLC. Accrual is continuing to 40 patients and updated response and survival data will be presented. No significant financial relationships to disclose.

Real-world data of osimertinib in the management of leptomeningeal metastases in EGFR mutant NSCLC: Light at the end of the tunnel?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21197-e21197
Author(s):  
Mansi Sharma ◽  
Shrinidhi Nathany ◽  
Satya Narayan ◽  
Pallavi Redhu ◽  
Parveen Jain ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Intrathecal Chemotherapy ◽  
Leptomeningeal Metastases ◽  
Second Line ◽  
First Line ◽  
Real World Data ◽  
Treatment Naïve ◽  
Egfr Mutant ◽  
Line Setting

e21197 Background: Presence of leptomeningeal metastases (LM) in NSCLC is indicative of aggressive disease and the incidence is as high as 9%-16% in the EGFR mutant subgroup. Traditionally, these patients had a dismal outcome with WBRT and intrathecal chemotherapy. Osimertinib crosses the blood brain barrier and is efficacious in the second line setting, as seen in BLOOM trial (LM ORR of 62%) and AURA program (LM ORR 55%). Osimertinib has also demonstrated CNS efficacy in the first line (FLAURA trial). This study is a retrospective review of cases with LM treated with osimertinib, and their response outcomes. Methods: 16 patients of EGFR mutant NSCLC developed LM at some point in their disease course and were treated with osimertinib. Clinical features and response outcomes were retrieved from medical record archives. Descriptive statistics were done using SPSS v23 software. LM PFS was defined as the time between 1st dose of osimertinib and date of progression in LM. LM OS was defined as the time between the first dose of osimertinib to the date of last follow up/death. ORR was defined as the percentage of cases showing CR/PR to osimertinib. Results: Median age was 61 years (range: 33-79) with 9 males and 7 females. Del19 mutations were seen in 9 patients and L858R in 7 patients. Only one patient was given WBRT prior to TKI. 6 patients with LM at diagnosis were given 1st line osimertinib. 3 (50%) progressed in LM and 3 (50%) showed partial response. Median LM PFS and median LM OS was not reached. ORR for osimertinib in the first line was 83.3%. 10 patients developed LM later in the course of the disease and median time to onset of LM was 12.47 months. Median LM PFS for osimertinib was 7.9 months (95% CI:3.2-8.3). Median LM OS was 8.2 months (95% CI: 2.6-19.8 months). ORR for osimertinib in the later line was 60%. Conclusions: This early experience reveals superior efficacy of osimertinib in LM with an excellent LM ORR in the first line setting and concordant results with second line BLOOM Study. Despite the small numbers in this study, this report becomes clinically relevant owing to the rarity of LM occurrence and paucity of available data. Efficacy of osimertinib in EGFR treatment-naive patients with LM requires further investigation and a larger prospective trial with a longer follow up may help confirm our preliminary findings.

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