Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial

Hanna, Nasser H.; Kaiser, Rolf; Sullivan, Richard; Aren, Osvaldo Rudy; Ahn, Myung Ju; Tiangco, B.; Voccia, Isabelle; Pawel, Joachim von; Kovčin, Vladimir; Agulnik, J.; Gaschler‐Markefski, Birgit; Barrueco, José; Sikken, Patricia; Schloss, Charles; Kim, Joo Hang

doi:10.1016/j.lungcan.2016.10.011

Cited by 74 publications

(76 citation statements)

References 23 publications

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“…However, increased toxicity was observed during bevacizumab treatment and class‐related adverse events including hypertension, proteinuria, febrile neutropenia and life‐threatening pulmonary hemorrhage, particularly in squamous NSCLC 8, 9, 10. The approval of ramucirumab and nintedanib has provided new options for NSCLC patients who progressed on initial treatment, with improved OS and tolerable toxicity when combined with standard second‐line chemotherapy 11, 12, 13. More recently, anlotinib, a novel multitarget tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), platelet‐derived growth factor receptor‐β (PDGFRβ), and fibroblast growth factor receptor‐1 (FGFR1), has provided significant progression‐free survival (PFS) and OS benefits as third‐line treatment 14…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Zhou

Zuo²,

et al. 2018

Thoracic Cancer

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BackgroundRecombinant human endostatin (rh‐endostatin) plus standard chemotherapy in advanced non‐small cell lung cancer (NSCLC) patients has shown improved efficacy; however, it is unclear whether it is effective and safe when added to pemetrexed/cisplatin and used as maintenance therapy.MethodsWe retrospectively evaluated the data of untreated NSCLC patients administered rh‐endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin. The primary endpoint was progression‐free survival (PFS).ResultsFifty‐six and 39 patients received rh‐endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, and 34 and 29 underwent maintenance treatment, respectively. The median PFS was 10 months (95% confidence interval [CI] 5.85–14.15) in the rh‐endostatin and 8.2 months (4.04–12.36) in the chemotherapy group, but the difference was not statistically significant (P = 0.13). In patients administered maintenance treatment, rh‐endostatin plus pemetrexed was associated with prolonged PFS compared to single‐agent pemetrexed when PFS was calculated from first dosing (13.7 [9.41–17.99] vs. 8.2 [4.16–12.24]; P = 0.032); however, PFS did not differ between the groups (hazard ratio 0.618; 95% CI 0.368–1.038; P = 0.069) after adjusting for clinical factors. No difference was observed in the objective response rate between the groups (48.2% vs. 38.5%; P = 0.346), with the exception of men (62.1% vs. 33.3%; P = 0.032) or in the incidence of drug‐related or grade 3–4 adverse events.ConclusionIn previously untreated, advanced‐stage NSCLC patients, first‐line treatment with pemetrexed/cisplatin plus rh‐endostatin did not prolong PFS or overall survival when compared to pemetrexed/cisplatin, but a trend of improved PFS was observed in patients administered maintenance rh‐endostatin plus pemetrexed.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Zhou

Zuo²,

et al. 2018

Thoracic Cancer

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“…There was no difference in OS. Nintedanib/pemetrexed resulted in a higher incidence of grade 3 elevated transaminases and diarrhea compared with placebo/pemetrexed, but no difference in hypertension, bleeding, or thrombosis [28].…”

Section: Nintedanibmentioning

confidence: 87%

“…The LUME-Lung 2 study investigated the efficacy and safety of nintedanib (200 mg twice daily, days 2-21) plus pemetrexed in non-sq patients with recurrent disease [28]. Based on a preplanned futility analysis, recruitment was stopped early.…”

Section: Nintedanibmentioning

confidence: 99%

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Janning

Loges

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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“…Selective identification of patients that may benefit from anti-angiogenic agents based on biomarkers has been a significant focus of research interest for more than a decade. A recent study conducted to identify predictive clinical biomarkers for nintedanib using data from 2 large second-line NSCLC Phase III trials showed that time since the initiation of first-line therapy is the only prognostic and predictive clinical biomarker for nintedanib and docetaxel combination therapy [6,9,10]. Two phase 3 clinical studies of second-line therapy in NSCLC adenocarcinoma using nintedanib or ramucirumab included < 5% EGFR-mutant NSCLC cases and the LUME-Lung 1 trial did not evaluate EGFR mutation status [6,10,11].…”

Section: Discussionmentioning

confidence: 99%

Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program

Hong

Kim

et al. 2018

Oncology

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Objectives: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. Methods: Docetaxel was administered either 75 or 37.5 mg/m² on D1, D8 q every 3 weeks for 4–6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. Results: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(–), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(–), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. Conclusions: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

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Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial

Cited by 74 publications

References 23 publications

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program

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