A randomized phase II trial of erlotinib or erlotinib and bevacizumab in patients with advanced EGFR mutant non-small cell lung cancer (NSCLC)

Stinchcombe, Thomas E.; Wang, X.; Bertino, Erin M.; Weiss, Jared; Bazhenova, Lyudmila; Gu, Lin; Lau, Christie J.; Paweletz, Cloud P.; Jaslowski, Anthony J.; Gerstner, Gregory J.; Baggstrom, Maria Q.; Graziano, Stephen L.; Bearden, James D.; Vokes, Everett E.

doi:10.1093/annonc/mdy292.066

Cited by 4 publications

(5 citation statements)

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“…50 In contrast, another recent phase II trial (N ¼ 88) did not report significant improvement in PFS with erlotinib plus bevacizumab versus with erlotinib monotherapy (17.9 months and 13.5 months, respectively [HR ¼ 0.87, 95 CI: 0.54-1.43, p ¼ 0.59]) in patients with EGFR-mutant NSCLC, with the survival data still immature. 51 Limited number of patients and treatment postprogression may influence the final results of this study. Results of the ongoing phase III NEJ026 trial (N ¼ 224) comparing erlotinib plus bevacizumab with erlotinib alone endorse the PFS benefit of this combination (16.9 versus 13.3 months [HR ¼ 0.605, 95% CI: 0.417-0.877, p ¼ 0.0157]), with OS data not yet available.…”

Section: Targeted Therapies In Advanced Nsclcmentioning

confidence: 99%

“…Key results from the recent first-line EGFR TKIs studies are summarized in Table 3. [43][44][45][48][49][50][51][52][53] Mechanisms of Acquired Resistance. The development of resistance to first-line treatment with gefitinib, erlotinib, or afatinib is inevitable, and the T790M mutation accounts for more than 50% of resistance followed by MNNG HOS Transforming gene (MET) amplification, activation of other bypass pathways, and histologic transformation to SCLC.…”

Section: Targeted Therapies In Advanced Nsclcmentioning

confidence: 99%

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Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Remón

Ahn

Girard

et al. 2019

Journal of Thoracic Oncology

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In 2018 research in the field of advanced NSCLCs led to an expanded reach and impact of immune checkpoint inhibitors (ICIs) as part of a frontline treatment strategy, regardless of histologic subtype, with ICI use extended to include stage III disease, shifting the prognosis of all these patients. This new standard first-line approach opens a gap in standard second-line treatment, and older combinations may again become standard of care after progression during treatment with an ICI. The characterization of predictive *Corresponding author. Disclosure: Dr. Remon reports honoraria from Merck Sharp and Dohme and Boehringer Ingelheim for serving as an adviser, speaker fees from Pfizer, personal fees and nonfinancial support from Ose Immunotherapeutics, personal fees from Bristol-Myers Squibb and AstraZeneca for travel and serving as an adviser, and reimbursement fees for travel expenses from Roche outside the submitted work. Dr. Ahn reports personal fees from AstraZeneca, Takeda,

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Section: Targeted Therapies In Advanced Nsclcmentioning

confidence: 99%

Section: Targeted Therapies In Advanced Nsclcmentioning

confidence: 99%

Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Remón

Ahn

Girard

et al. 2019

Journal of Thoracic Oncology

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“…Safety is also a very important part of treatment evaluation, and previously published results show that combination treatment with bevacizumab increases the risks of SAEs. [9][10][11][12][13] Patients with NSCLC are often diagnosed at an advanced stage, and need better treatment choices to effectively improve their prognosis. According to the results, combination therapy can effectively prolong PFS and improve ORR.…”

Section: Discussionmentioning

confidence: 99%

“…The results indicate that combined treatment significantly prolongs PFS, and increases ORR, but that there was no substantial difference in OS between the control and experimental groups. Safety is also a very important part of treatment evaluation, and previously published results show that combination treatment with bevacizumab increases the risks of SAEs 9–13 . Patients with NSCLC are often diagnosed at an advanced stage, and need better treatment choices to effectively improve their prognosis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of bevacizumab combined with EGFR‐TKIs in advanced non‐small cell lung cancer: A meta‐analysis

Yang

Wang

et al. 2021

Thoracic Cancer

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Background The aim of this study was to estimate the efficacy and safety of bevacizumab combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non‐small cell lung cancer (NSCLC) patients. Methods We searched randomized controlled trials (RCTs) on bevacizumab combined with EGFR TKIs in the NSCLC Cochrane Library, Web of Science, PubMed and Embase. The data were extracted and assessed according to the Cochrane Handbook. We calculated the hazard ratio (HR), risk ratio (RR), and confidence interval (CI), and accomplished this meta‐analysis with Stata 14 software. Results Of 1301 articles scanned, five articles were involved in this meta‐analysis. We determined that compared with using EGFR TKIs alone, combination treatment significantly prolongs progression‐free survival (PFS) (HR = 0.61, 95% CI = 0.52–0.70; p < 0.001), and increases the objective response rate (ORR) (RR = 1.15, 95% CI: 1.01–1.30, p = 0.10). However, there was no significant difference in overall survival (OS) between the two groups (HR = 0.95, 95% CI = 0.78–1.11; p = <0.001) and combination treatment increases the risks of serious adverse events (SAEs) (RR = 1.58, 95% CI: 1.21–2.05, p = 0.002). Conclusions Bevacizumab combined with EGFR‐TKI significantly improves PFS and ORR in patients with advanced NSCLC, but there is no substantial difference in OS and increase the risks of serious adverse events.

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“…Results from preclinical and clinical trials point to substantially improved progression-free survival in patients with EGFR-mutant NSCLC receiving combined EGFR TKIs and angiogenic therapy. However, this combined therapeutic approach has been characterized by an increased incidence of adverse reactions of grades 3-5 [41,[46][47][48][49][50][51][52][53]. Nanomedicines can be used as tools for improved localization of combination therapy at the site of action, improving the outcome and decreasing the adverse effects.…”

Section: Target Independentmentioning

confidence: 99%

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

Gorachinov¹,

Mraiche²,

Moustafa³

et al. 2023

Beilstein J. Nanotechnol.

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Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

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A randomized phase II trial of erlotinib or erlotinib and bevacizumab in patients with advanced EGFR mutant non-small cell lung cancer (NSCLC)

Cited by 4 publications

References 0 publications

Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Efficacy and safety of bevacizumab combined with EGFR‐TKIs in advanced non‐small cell lung cancer: A meta‐analysis

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

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