Systemic Therapy of Advanced Bronchioloalveolar Cell Carcinoma: Challenges and Opportunities

2005 ◽  
Vol 23 (14) ◽  
pp. 3288-3293 ◽  
Author(s):  
Vincent A. Miller ◽  
Fred R. Hirsch ◽  
David H. Johnson
Keyword(s):  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Small Body ◽  
Clinical Manifestations ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Careful Study ◽  
Phase Ii Trials ◽  
Egfr Tyrosine Kinase ◽  
Bronchioloalveolar Cell Carcinoma

Bronchioloalveolar cell carcinoma (BAC) has fascinated physicians with its unique epidemiology, pathology, clinical manifestations, and natural history when compared with other non–small-cell lung cancer (NSCLC) subtypes. However, the relative rarity of pure BAC as defined by the WHO, and the inconsistent definitions used in various series, has limited systematic study of this entity. Retrospective and prospective studies suggest that patients with BAC treated with cytotoxic chemotherapy have a longer median survival than those with other subtypes of NSCLC. However, the widely accepted view that BAC is less chemosensitive than other NSCLCs is not clearly supported by the small body of available literature. Antitumor activity of cytotoxic agents and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been documented in phase II trials but no phase III trials have been conducted in this disease. The observation that profound responses to gefitinib and erlotinib often occurred in NSCLC patients with BAC, and that EGFR tyrosine kinase domain mutations were identified in large part by careful study of such patients, serves as a paradigm for translational research in this disease. The recognition that pure BAC and adenocarcinoma with BAC features behave similarly and as such represent a relatively common entity will facilitate accrual to BAC specific studies. Alternatively, stratification of these histologic subtypes in broader clinical trials in NSCLC is warranted. However, for either strategy to succeed in advancing our understanding of the molecular biology of BAC, it must be accompanied by central pathologic review with detailed classification of such, and of adequate tissue for measurement of known or putative targets of action of the agent under study.

Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L

2016 ◽  
Vol 34 (27) ◽  
pp. 3248-3257 ◽  
Author(s):  
Yoshiko Urata ◽  
Nobuyuki Katakami ◽  
Satoshi Morita ◽  
Reiko Kaji ◽  
Hiroshige Yoshioka ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Performance Status ◽  
Phase Iii ◽  
Survival Times ◽  
Egfr Tyrosine Kinase ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Egfr Tkis

Purpose The epidermal growth factor receptor (EGFR) tyrosine kinase has been an important target for non–small-cell lung cancer. Several EGFR tyrosine kinase inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs. This randomized phase III study was conducted to investigate the difference between these two EGFR-TKIs. Patients and Methods Previously treated patients with lung adenocarcinoma were randomly assigned to receive gefitinib or erlotinib. This study aimed to investigate the noninferiority of gefitinib compared with erlotinib. The primary end point was progression-free survival (PFS). Results Five hundred sixty-one patients were randomly assigned, including 401 patients (71.7%) with EGFR mutation. All baseline factors (except performance status) were balanced between the arms. Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8 and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively. Median PFS times in EGFR mutation–positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to 1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for erlotinib). Conclusion The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria.

Design and Synthesis of Quinazolinone Tagged Acridones as Cytotoxic Agents and Their Effects on EGFR Tyrosine Kinase

2014 ◽  
Vol 347 (9) ◽  
pp. 624-634 ◽  
Author(s):  
Yarlagadda Rajesh Babu ◽  
Mantripragada Bhagavanraju ◽  
Gade Deepak Reddy ◽  
Godefridus J. Peters ◽  
Velivela V. S. Rajendra Prasad
Keyword(s):  
Tyrosine Kinase ◽  
Cytotoxic Agents ◽  
Design And Synthesis ◽  
Egfr Tyrosine Kinase

Combination anti-angiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 630-630
Author(s):  
Andrew L. Laccetti ◽  
Minas P. Economides ◽  
Aradhana M. Venkatesan ◽  
Jianjun Gao ◽  
Eric Jonasch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Retrospective Analysis ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Case Series ◽  
Phase Iii ◽  
Line Treatment ◽  
First Case

630 Background: Emerging phase III data support combination antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) as front line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol experience and later line treatment with this therapeutic approach including tolerance, response and survival. Methods: We conducted a retrospective analysis of mRCC patients (pts) who received combination TKI-IO between 11/2015 and 05/2018 at MD Anderson Cancer Center. Chart review detailed baseline characteristics, TKI-IO treatment, toxicity and survival. An independent radiologist, blinded to pts history and clinical data, assessed radiographic response using RECIST v1.1. Results: 36 mRCC pts were identified for study inclusion: median (med) age 63.5 years, 72% clear cell histology, 53% intermediate risk (19% good, 28% poor) by IMDC, med metastatic sites 2, med prior therapies 2, previous TKI 94% and previous IO 47%. Combinations included nivolumab (nivo)-cabozantinib (15), nivo-low dose pazopanib(ldP) (13), nivo-axitinib (5), nivo-lenvatinib (2) and pembrolizumab-axitinib (1). Median time on TKI-IO was 5.6 months (m) (95% CI: 5.2 - 7.7). 56% of pts initiated TKI prior to IO addition at progression and 36% of pts initiated IO prior to TKI addition. ORR was 35% (29% PR and 6% CR); disease control rate was 78% (43% stable disease). With med follow-up of 8.0 m (95% CI: 6.4 – 9.4), med PFS was 7.7 m (95%CI: 5.8 - 9.5), med OS was not reached. Med PFS for pts receiving nivo-ldP was not reached. TKI-IO therapy was well tolerated with only 1 pt demonstrating grade 3 or 4 immune related toxicity (nephritis). 92% of pts experienced any grade of adverse events (ADE) with ADE of interest as follows: diarrhea (25%), hypothyroidism (17%), and pneumonitis (8%). Conclusions: To our knowledge, this is the first case series of off-label combinations of TKI-IO for mRCC. TKI-IO, particularly nivo-ldP, is safe, well tolerated and efficacious. Although further prospective research is essential, TKI-IO could be considered for select mRCC patients, particularly in the setting of TKI or IO refractory disease.

Activity of lenvatinib plus everolimus combination in a heavily pretreated patient with papillary renal cell carcinoma: a case report

2020 ◽  
Vol 106 (6) ◽  
pp. NP79-NP83
Author(s):  
Teresa Zielli ◽  
Letizia Gnetti ◽  
Sebastiano Buti
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitors ◽  
Papillary Renal Cell Carcinoma ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Histologic Subtype ◽  
Heavily Pretreated ◽  
Common Histologic Subtype

Background: Papillary renal cell carcinoma (pRCC) represents the second most common histologic subtype of renal cell carcinoma and comprises 2 subtypes. Prognosis for type 2 is associated with poor clinical outcome. Current guidelines are based on phase II trials, phase III trials in patients with clear cell histology, or retrospective data. Case description: To our knowledge, we describe for the first time a case of a patient with heavily pretreated metastatic pRCC who benefited from the combination of lenvatinib plus everolimus for more than 2 years. Conclusion: According to immunohistologic and biological findings in our patient both on primary tumor and liver metastasis, we hypothesize that selected patients with metastatic pRCC, progressed to standard/available treatments (including angiogenic drugs, mTOR inhibitors, and immunotherapy) and dissociated response to everolimus, could benefit from adding lenvatinib to everolimus.

scholarly journals Therapies after first-line afatinib in patients with EGFRm+ NSCLC in Japan: retrospective analysis of LUX-Lung 3

2020 ◽  
Vol 16 (4) ◽  
pp. 49-60
Author(s):  
Hiroshige Yoshioka ◽  
Terufumi Kato ◽  
Isamu Okamoto ◽  
Hiroshi Tanaka ◽  
Toyoaki Hida ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Japanese Patients ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
Egfr Tyrosine Kinase

Aim: Acquired resistance to EGFR tyrosine kinase inhibitors is inevitable in non-small-cell lung cancer. To inform subsequent treatment decisions, we retrospectively assessed therapies following afatinib in Japanese patients from LUX-Lung 3. Patients & methods: LUX-Lung 3 was a randomized, open-label, Phase III study of afatinib versus cisplatin/pemetrexed in treatment-naive patients with EGFR mutation-positive ( EGFRm+) advanced lung adenocarcinoma. Results: Among 47 Japanese patients who discontinued first-line afatinib, 91/81/62% received ≥one/two/three subsequent therapies. The most common second-line therapies were platinum-based chemotherapy (38%) and a first-generation EGFR tyrosine kinase inhibitor (17%). Median overall survival (afatinib vs cisplatin/pemetrexed) was 47.8 versus 35.0 months (not significant). Conclusion: First-line afatinib does not appear to diminish suitability for subsequent therapies in EGFRm+ non-small-cell lung cancer.

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