Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC).

Kabbinavar, Fairooz; Miller, Vincent A.; Johnson, Benjamin; O’Connor, Paula G.; Soh, Chang-Heok; Investigators, Atlas

doi:10.1200/jco.2010.28.15_suppl.7526

Cited by 84 publications

(55 citation statements)

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“…Secondary objectives included determining the proportion of patients who showed FDG-and FLT-PET response on day 14 and day 56 among all patients, and among those with CT stable disease, and evaluating the safety of FLT. Exploratory objectives included assessment of the relationship between FDG-and FLT-PET response and tumor characteristics, particularly EGFR-and KRAS-related markers (30)(31)(32)(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib

Mileshkin

Hicks

Hughes

et al. 2011

Clinical Cancer Research

117

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Purpose: Assessing clinical activity of molecularly targeted anticancer agents, especially in the absence of tumor shrinkage, is challenging. To evaluate on-treatment 18F-fluorodeoxyglucose (FDG) and/or 18F-fluorodeoxythymidine (FLT) positron emission tomography (PET) for this purpose, we conducted a prospective multicenter trial assessing PET response rates and associations with progression-free (PFS) and overall survival (OS) in 2nd/3rd-line non-small-cell lung cancer patients treated with erlotinib.Experimental Design: PET/computed tomography (CT) scans were conducted at baseline, day (d)14 and d56 after the first daily erlotinib dose, with diagnostic CT at baseline and d56 (all scans centrally reviewed). PET partial metabolic response (PMR) was defined as a mean decrease (in 5 lesions/patient) of 15% or more maximum standardized uptake value. PFS was investigator-determined.Results: Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13 of 51 (26%) FDG-evaluable patients had PMR at d14, as did 9 of 50 (18%) FLT-evaluable patients. Four (7.8%) showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET with 3 PMRs by d14 FLT-PET. Three of the 4 patients with CT PR had evaluable archival tumor tissue; all 3 had epidermal growth factor receptor mutations. D14 and d56 PMRs by FDG or FLT were associated with improved PFS; HRs for PET responders versus nonresponders were 0.3 to 0.4. D14 FDG-PET PMR was associated with improved OS (P ¼ 0.03) compared with FDG-PET nonresponders.Conclusion: Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent Response Evaluation Criteria in Solid Tumors response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects. Clin Cancer Res; 17(10); 3304-15. Ó2011 AACR.

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Section: Introductionmentioning

confidence: 99%

Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib

Mileshkin

Hicks

Hughes

et al. 2011

Clinical Cancer Research

117

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“…Progression-free survival was improved in the erlotinib and bevacizumab maintenance arm (4.8 months vs. 3.7 months, p = 0.0012) 24 . No significant difference in os was found (15.9 months vs. 13.9 months, p = 0.2686), which may be a reflection of the broader availability of erlotinib upon progression (received in 40% of the placebo group) 35 . A benefit in pfs similar to that seen in the saturn trial was observed in the EGFR activating mutation-positive and -negative subgroups (hr: 0.44 and 0.85 respectively).…”

Section: Erlotinibmentioning

confidence: 80%

Personalized Choice of Maintenance Therapies in Non-Small-Cell Lung Cancer

Blais

Corrales-Rodriguez²

2012

Current Oncology

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Platinum-based combinations currently remain the preferred approach in the first-line setting 5,6 . Further studies have also established a role for second-line and, in some instances, third-line therapy with agents such as docetaxel, pemetrexed, and erlotinib. These advances have resulted in median survivals of 10-12 months in contemporary studies.Although second-line therapies have improved overall survival, up to 50% of patients completing first-line treatment become ineligible for further treatment, mostly because of significant tumour progression or rapid decline in performance status (or both). This reality has pushed many investigators to study earlier use of second-line therapy in the form of maintenance therapy. First-line maintenance therapy is defined in the setting of patients not experiencing progression after a first-line platinum-containing regimen. Some investigators have studied the prolonged use of the platinum partner from the firstline regimen in what has been called "continuation maintenance"; others have studied the use of a noncross-resistant agent after induction, which has been termed "switch maintenance" 7 . Clinically significant results generated from many studies have raised the question of personalized approaches based on clinical, pathologic, and molecular features of the cancer.Recognizing the importance of the pathologic and molecular features of lung cancer, the Canadian consensus biomarker group recently recommended that histologic subtyping of nsclc be performed in every case 8 . For example, non-squamous histology was shown to be predictive of superiority for the pemetrexed arm over the standard arm in three large randomized studies 6,9 . Prediction of serious bleeding toxicity with bevacizumab in squamous cell lung cancer patients was also suggested in an early phase ii trial, leading to the eventual exclusion of patients with squamous histology from most trials testing that drug 10,11 . Thus, the distinction between squamous and non-squamous histology has become fundamental in the management of nsclc.Similarly, the identification of specific "druggable" targets such as mutated EGFR and overexpressed ABSTRACTLung cancer has become a leading cause of cancerrelated death in the world. Patient survival has improved with the introduction of new chemotherapy regimens and targeted drugs, but still, because of tumour progression or deterioration in performance status, a high percentage of patients do not receive more than one line of treatment. Given this situation, studies of maintenance therapies have begun, with results that have led to the clinical use of various drugs in a maintenance scenario. Additionally, results obtained in various clinical trials have raised the question of personalized approaches based on the clinical, pathologic, and molecular features of the cancer-not only in the initial approach, but also in the context of maintenance. Overall, the survival benefit seen with maintenance treatment has introduced a new therapy option that should be considered and discu...

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“…The ATLAS trial studied the combination of bevacizumab and erlotinib as a maintenance strategy after the SATURN study had shown an improved PFS and OS with erlotinib alone [Miller et al 2009;Kabbinavar et al 2010]. In ATLAS, patients received four cycles of platinum-based chemotherapy with bevacizumab and those with at least stable disease (SD) continued bevacizumab with or without erlotinib versus placebo.…”

Section: Combination Maintenancementioning

confidence: 99%

Maintenance treatment after induction therapy in non-small cell lung cancer: latest evidence and clinical implications

Gentzler

Patel

2013

Ther Adv Med Oncol

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Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC. Therapies that have been studied in this setting in randomized trials to date include chemotherapy and molecularly targeted agents. Following the development of multiple new agents that show activity in NSCLC and have a tolerable side-effect profile, there has been increasing interest in utilizing them to maintain response to initial therapy after treatment with platinum-based doublets. Two effective strategies have evolved: continuation and switch maintenance. Despite improvements in progression-free survival and often overall survival on multiple clinical trials, there remains considerable controversy around this treatment paradigm. Here, we briefly outline the evolution of this treatment strategy and examine the available data, including recently updated data from the PARAMOUNT, AVAPERL, and PointBreak maintenance trials. Ultimately, the decision to use maintenance chemotherapy requires a nuanced discussion between the patient and physician that adequately assesses benefits of prolonged therapy and impact in terms of toxicity, quality of life, and financial cost.

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Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC).

Cited by 84 publications

References 0 publications

Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib

Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib

Personalized Choice of Maintenance Therapies in Non-Small-Cell Lung Cancer

Maintenance treatment after induction therapy in non-small cell lung cancer: latest evidence and clinical implications

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