Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial

Wakelee, Heather A.; Dahlberg, Suzanne E.; Keller, Steven M.; Tester, William J.; Gandara, David R.; Graziano, Stephen L.; Adjei, Alex A.; Leighl, Natasha B.; Aisner, Seena C.; Rothman, Jan M.; Patel, Jyoti D.; Sborov, Mark D.; McDermott, Ray; Pérez-Soler, Román; Traynor, Anne M.; Butts, Charles; Evans, Tracey L.; Shafqat, Atif; Chapman, Andrew E.; Kasbari, Samer S.; Horn, Leora; Ramalingam, Suresh S.; Schiller, Joan H.

doi:10.1016/s1470-2045(17)30691-5

Cited by 145 publications

(113 citation statements)

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“…In the E1505 trial, patients were randomly assigned to receive cisplatin in combination with the investigators' choice of vinorelbin, docetaxel, gemcitabine, or pemetrexed with or without bevacizumab (15 mg/kg). The results of this trial suggested that addition of bevacizumab to chemotherapy does not improve OS or PFS in the adjuvant setting [19]. Notably, these results are similar to adjuvant trials with bevacizumab in other cancers [20,21].…”

Section: Bevacizumab In Early-stage Nsclcsupporting

confidence: 60%

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Janning

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2018

Oncol Res Treat

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Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Different targeted therapies and the introduction of immunotherapy have successfully improved outcome for patients with non-small lung cancer (NSCLC). Anti-angiogenic drugs are an essential component in the treatment of NSCLC patients. The vascular endothelial growth factor (VEGF)-A antibody bevacizumab is approved for first-line treatment of advanced-stage patients in combination with platinum-based chemotherapy. Ramucirumab, a VEGF receptor antibody, and nintedanib, an anti-angiogenic multi-tyrosine kinase inhibitor, are approved for second-line treatment in combination with docetaxel. This review provides a summary of pivotal trials with anti-angiogenic drugs in NSCLC in different settings. We give an overview of how to position anti-angiogenic therapy in the current treatment algorithms and highlight future directions. The identification of predictive biomarkers for patient selection could improve the success of anti-angiogenic drugs and represents an important area of research. In addition, novel therapeutic targets including endothelial metabolomic intermediates and cellular components of the tumor microenvironment could lead to the identification of innovative new targets besides the VEGF axis.

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Section: Bevacizumab In Early-stage Nsclcsupporting

confidence: 60%

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Janning

Loges

2018

Oncol Res Treat

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“…7 Perioperative platinum-based chemotherapy is associated with a survival rate that is only 5.4 percentage points higher than that with surgery alone, with rates of toxic effects of grade 3 or higher of more than 60%. 8,9 PD-1 pathway blockade in patients with early-stage lung cancer may have enhanced antitumor effects owing to greater fitness of host immunity and reduced tumor clonal heterogeneity. 10 Neoadjuvant immunotherapy is attractive, since the primary tumor may be leveraged as an antigen source for expansion and activation of tumor-specific T cells and systemic surveillance of micrometastases.…”

mentioning

confidence: 99%

Neoadjuvant PD-1 Blockade in Resectable Lung Cancer

et al. 2018

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BACKGROUND Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non–small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. METHODS In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses. RESULTS Neoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab. CONCLUSIONS Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute–Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621.)

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“…• Consider administering cisplatin/docetaxel to limit time in hospital, as it avoids day 8 administration of gemcitabine or vinorelbine, and has equivalent efficacy. In non-squamous nonsmall cell lung cancer (NSCLC), cisplatin/pemetrexed is an equally efficacious alternative [8]. • In patients with an activating epidermal growth factor receptor (EGFR) mutation, consider a 1-year course of daily oral EGFR tyrosine kinase inhibitor (TKI) as an alternative to adjuvant chemotherapy (currently no phase 3 evidence of superiority available).…”

Section: Adjuvant Chemotherapymentioning

confidence: 99%