A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer

Marrone, Kristen A.; Zhou, Xian; Forde, Patrick M.; Purtell, Michael; Brahmer, Julie R.; Hann, Christine L.; Kelly, Ronan J.; Coleman, Barbara; Gabrielson, Edward; Rosner, Gary L.; Ettinger, David S.

doi:10.1634/theoncologist.2017-0465

Cited by 79 publications

(75 citation statements)

References 25 publications

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“…2,3 Outcomes for patients with metastatic NSCLC are poor, with only 4% of patients surviving 5 years after diagnosis. 6,7 Atezolizumab is an IgG1 monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 and B7-1 (also known as CD80) receptors. 6,7 Atezolizumab is an IgG1 monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 and B7-1 (also known as CD80) receptors.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Before the introduction of targeted therapies and immunotherapy, platinum-doublet chemotherapy with or without bevacizumab was the standard of care for previously untreated patients with metastatic, nonsquamous NSCLC. 6,7 Atezolizumab is an IgG1 monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 and B7-1 (also known as CD80) receptors. 4 The IMpower150 trial evaluated the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) for previously untreated patients with metastatic, nonsquamous NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Wan

Luo

Tan

et al. 2019

Cancer

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BACKGROUND:The IMpower150 trial found that adding atezolizumab to the combination of bevacizumab and chemotherapy improved survival for patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC). However, considering the high cost of immunotherapy, there is a need to assess its value by considering both efficacy and cost. The current study evaluated the cost-effectiveness of atezolizumab in the first-line setting for the treatment of patients with metastatic NSCLC from the US payer perspective. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) with the combination of bevacizumab, carboplatin, and paclitaxel (BCP) and carboplatin and paclitaxel (CP) in the first-line treatment of patients with metastatic NSCLC. Life-years (LYs), qualityadjusted LYs (QALYs), and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: ABCP provided an additional 0.413 QALYs (0.460 LYs) and 0.738 QALYs (0.956 LYs), respectively, compared with BCP and CP. The corresponding incremental costs were $234,998 and $381,116, respectively. The incremental cost-effectiveness ratio for ABCP was $568,967 per QALY compared with BCP and $516,114 per QALY compared with CP. The subgroup analysis demonstrated that PD-L1 expression of ≥50% on tumor cells (TC3) or ≥10% on immune cells (IC3) decreased the incremental cost-effectiveness ratio to $464,703 per QALY. CONCLUSIONS: From the perspective of the US payer, ABCP is estimated to not be cost-effective compared with BCP or CP in the first-line setting for patients with metastatic, nonsquamous NSCLC at a willingness-to-pay threshold of $100,000 per QALY. Cancer 2019;125:3526-3534.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Wan

Luo

Tan

et al. 2019

Cancer

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“…The 1‐year PFS on arm A (carboplatin, paclitaxel, and bevacizumab with metformin) was 47% (95% CI, 25%‐88%), which exceeded the historical control 1‐year PFS of 15%. Median overall survival of patients treated on arm A was 15.9 months (95% CI, 8.4‐not available) and 13.9 months (95% CI, 12.7‐not available) on arm B (carboplatin, paclitaxel, and bevacizumab without metformin) . Disappointingly, the results indicated that there were no significant differences in toxicity between the two study arms.…”

Section: Combination Of Metformin With Antibodiesmentioning

confidence: 98%

Novel application of metformin combined with targeted drugs on anticancer treatment

et al. 2018

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The success of targeted drug therapies for treating cancer patients has attracted broad attention both in the academic community and social society. However, rapidly developed acquired resistance is becoming a newly recognized major challenge to the continuing efficiency of these therapies. Metformin is a well‐known natural compound with low toxicity derived from the plant French lilac. Our previous work has highlighted research progress of the combination of clinically applied chemotherapies and metformin by different mechanisms. We have also launched a study to combine metformin with the small molecule targeted drug gefitinib to treat bladder cancer using intravesical administration. Thus, in this minireview, we summarize recent achievements combining metformin with various targeted therapies. This work directs the potential clinical future by selecting available cancer patients and providing precise medicine by the combination of metformin and targeted drugs to overcome resistance and enhance therapeutic efficacies.

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“…It was approved in 2004 in combination with chemotherapy for metastatic colorectal cancer and now it is used in the treatment of numerous cancer types-metastatic breast cancer, renal cell carcinoma, advanced epithelial ovarian cancer, non-squamous NSCLC [75]. Combination of metformin with bevacizumab was found to be effective in the treatment of ovarian cancer and metastatic non-squamous NSCLC in combination with chemotherapy [76,77].…”

Section: Metformin: Combination With Targeted Therapiesmentioning

confidence: 99%

Metformin and Its Implication in Cancer Therapy

Mazilu¹,

Stănculeanu²,

Gheorghe³

et al. 2019

Metformin [Working Title]

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Metformin has been used for almost half a century as the first line of treatment for type 2 diabetes. Mechanisms of action are still incompletely known, recent studies have shown that metformin exerts its effects through several mechanisms, including the stimulation of AMP-activated protein kinase, decreasing production of cyclic AMP, inhibition of mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase and altering gut microbiota. In recent years, studies have shown that patients with type 2 diabetes mellitus have a lower risk of developing cancer, and patients with cancer and type 2 diabetes have a lower mortality. Experimental studies have demonstrated that metformin has anti-tumor activity by inhibiting mTORC1 signaling pathway and mitochondrial complex, inhibiting tumor growth and proliferation, and inducing cellular apoptosis. There are multiple studies showing that combination of metformin with different types of anti-cancer therapies may reduce toxicities and tumor resistance. This chapter is focused on the progress made in understanding the anti-tumor effect of metformin and its association with cancer therapy.

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A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer

Cited by 79 publications

References 25 publications

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Novel application of metformin combined with targeted drugs on anticancer treatment

Metformin and Its Implication in Cancer Therapy

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