Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial

Saito, Haruhiro; Fukuhara, Tatsuro; Furuya, Naoki; Watanabe, Kana; Sugawara, Shunichi; Iwasawa, Shunichiro; Tsunezuka, Yoshio; Yamaguchi, Ou; Okada, Morihito; Yoshimori, Kozo; Nakachi, Ichiro; Gemma, Akihiko; Azuma, Koichi; Kurimoto, Futoshi; Tsubata, Yukari; Fujita, Yuka; Nagashima, Hiromi; Asai, G.; Watanabe, Satoshi; Miyazaki, Masaki; Hagiwara, Koichi; Nukiwa, Toshihiro; Morita, Satoshi; Kobayashi, Kunihiko; Maemondo, Makoto

doi:10.1016/s1470-2045(19)30035-x

Cited by 478 publications

(557 citation statements)

References 33 publications

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“…The opportunities to use liquid biopsy for an analysis of the T790M status may thus also become limited. However, recent studies have shown that combination therapy with a first‐generation EGFR TKI and either platinum‐based chemotherapy or bevacizumab confers a significant survival advantage in comparison with EGFR TKI monotherapy . Moreover, a recent retrospective analysis of the FLAURA trial that examined the mechanisms of acquired resistance to first‐line osimertinib in patients with EGFR ‐mutated advanced NSCLC found that the C797S mutation of EGFR was present at a low frequency (7%) in patients who developed resistance.…”

Section: Discussionmentioning

confidence: 99%

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Takahama

Azuma

Shimokawa

et al. 2020

Cancer

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BACKGROUND: Liquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non-small cell lung cancer (NSCLC) who develop resistance to first-or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance-conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients. METHODS: Eligible patients had advanced or recurrent NSCLC with known TKI-sensitizing mutations of EGFR, had documented disease progression after treatment with at least 1 first-or second-generation EGFR TKI, and were positive for the T790M mutation in plasma according to the Cobas EGFR Mutation Test v2 (Roche Diagnostics) or droplet digital polymerase chain reaction analysis. Patients were treated with osimertinib (80 mg/d) until disease progression. The primary endpoint was the overall response rate (ORR) in patients positive for T790M in plasma by the Cobas assay. RESULTS: Between June 2016 and November 2017, 276 patients were screened for their T790M status with a liquid biopsy. Seventy-four patients were positive for T790M in plasma, and 53 of these individuals were enrolled in the study. The ORR for evaluable patients positive for T790M in plasma by the Cobas assay (n = 49) was 55.1% (95% confidence interval [CI], 40.2%-69.3%). The median progression-free survival for all evaluable patients (n = 52) was 8.3 months (95% CI, 6.9-12.6 months). CONCLUSIONS: The results demonstrate the utility of liquid biopsy for the detection of T790M with the Cobas EGFR Mutation Test v2. Plasma genotyping with this assay is informative for treatment selection in clinical practice when tumor sampling is not feasible.

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Section: Discussionmentioning

confidence: 99%

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Takahama

Azuma

Shimokawa

et al. 2020

Cancer

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“…Similar to many other carcinomas, NSCLC is united by having multiple genetic abnormalities, such as the epidermal growth factor receptor (EFGR) and c-ros oncogene 1 (ROS1) mutations, and those genetic features also contribute to the improvement pf NSCLC management. [13][14][15][16] Besides these altered genes, a diverse class of protein biomarkers also exist in the development of individualized treatment of NSCLC, and there have been studies indicate that combining biomarkers may have more satisfactory effect in the diagnosis and prognosis in NSCLC patients compared with a single genetic or protein biomarker. 17 Hence, researching for more biomarkers which could reinforce the detection rate and prognosis of patients with NSCLC is of urgent need.…”

Section: Discussionmentioning

confidence: 99%

AKIP1 expression in tumor tissue as a new biomarker for disease monitoring and prognosis in non‐small cell lung cancer: Results of a retrospective study

Liu¹,

Tian²,

Qin³

et al. 2019

Clinical Laboratory Analysis

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: A-kinase-interacting protein 1 (AKIP1) has been reported as an oncogenetic factor in multiple cancers; however, no study has reported its role in nonsmall cell lung cancer (NSCLC) yet. This study aimed to evaluate the expression of AKIP1, and its correlation with tumor characteristics as well as prognosis in patients with NSCLC.Methods: Four hundred and ninety patients with NSCLC who underwent resection were reviewed, and baseline clinical data were collected. AKIP1 expression in tumor tissue/paired adjacent tissue was detected by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were calculated. Results:A-kinase-interacting protein 1 expression was elevated in tumor tissue compared with paired adjacent tissue (P < .001), and high AKIP1 tumor tissue expression was correlated with poor pathological differentiation (P < .001), tumor size >5 cm (P = .001), lymph node metastasis (P = .016), higher TNM stages (P < .001), and abnormal CEA level (>5 ng/mL) (P = .035). DFS was worse in patients with tumor tissue AKIP1 high expression compared with patients who had AKIP1 low expression in total patients (P < .001), TNM stage I (P < .001) and TNM stage III (P < .001) patients. And the OS was also decreased in patients with AKIP1 high expression in total patients (P < .001), TNM stage I patients (P = .001) and TNM stage III patients (P = .004). Moreover, multivariate Cox's proportional hazards regression model analysis revealed that AKIP1 high expression was an independent predictive factor for worse DFS (P < .001) and OS (P < .001).

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“…Fei Liang expressed an important concern regarding lack of overall survival events (ie, deaths) for assessment of overall survival in the NEJ026 study 1 and in the combined analysis of NEJ026 and the JO25567 study. 2 We agree that overall survival is the most crucial factor to consider when evaluating benefits of drugs for patients with cancer.…”

Section: Nej026 Trial: Progression-free Survival Benefit Is Not Enougmentioning

confidence: 99%

Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial

Cited by 478 publications

References 33 publications

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

AKIP1 expression in tumor tissue as a new biomarker for disease monitoring and prognosis in non‐small cell lung cancer: Results of a retrospective study

NEJ026 trial: progression-free survival benefit is not enough – Author's reply

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