An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non–Small-Cell Lung Cancer

Spigel, David R.; Luft, Alexander; Depenbrock, H.; Ramlau, Rodryg; Khalil, Mazen; Kim, Joo Hang; Mayo, Carlos A.; Chao, Grace; Obasaju, Coleman K.; Natale, Ronald B.

doi:10.1016/j.cllc.2017.02.002

Cited by 17 publications

(19 citation statements)

References 23 publications

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“…Carbo + S-1 is only approved for the treatment of NSCLC in Asia, so, at this time, patients in other areas of the world do not have access to this therapy. Consistent with the evidence published by Spigel and colleagues (35), neci in combination with carbo + paclitaxel did not demonstrate improved efficacy; the FDA-approved combination with gem + cis remains the regimen that has demonstrated efficacy with necitumumab in squamous NSCLC. Despite the potentially improved outcomes of both carbo +S-1 and neci + gem + cis versus other comparators, the findings should be interpreted with caution due to the limitations stated here.…”

Section: Discussionsupporting

confidence: 74%

“…The evidence networks were analyzed via a single pairwise metaanalysis and as a series of indirect comparisons. Only two studies provided direct comparative data with neci +gem +cis (14,35). Adding to the limited data, indirect comparison estimates further increased uncertainty with each additional link in the evidence network.…”

Section: Discussionmentioning

confidence: 99%

“…Nine studies connected to the network for the PFS HR analysis (14,(28)(29)(30)34,35,37,38,61). Neci + gem + cis demonstrated longer PFS compared with all other comparators.…”

Section: Pfsmentioning

confidence: 99%

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First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis

et al. 2018

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Background: The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. Methods: The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995-2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. Results: The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Conclusions: Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis

et al. 2018

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“…In 2015, necitumumab was approved by the US FDA for the treatment of refractory metastatic squamous NSC lung cancer (NSCLC). In the study by Spigel et al ( 55 ), a total of 176 patients were enrolled and randomized to either the necitumumab group or the chemotherapy alone group. Their results show that necitumumab and chemotherapy improve survival in patients with advanced squamous NSCLC.…”

Section: Anti-tumor Mechanisms and Effects Of Egfr Mabsmentioning

confidence: 99%

The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells

et al. 2020

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Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor involved in homeostatic regulation of normal cells and carcinogenesis of epithelial malignancies. With rapid development of the precision medicine era, a series of new therapies targeting EGFR are underway. Four EGFR monoclonal antibody drugs (cetuximab, panitumumab, nimotuzumab, and necitumumab) are already on the market, and a dozen other EGFR monoclonal antibodies are in clinical trials. Here, we comprehensively review the newly identified biological properties and anti-tumor mechanisms of EGFR monoclonal antibodies. We summarize recently completed and ongoing clinical trials of the classic and new EGFR monoclonal antibodies. More importantly, according to our new standard, we re-classify the complex evolving tumor cell resistance mechanisms, including those involving exosomes, non-coding RNA and the tumor microenvironment, against EGFR monoclonal antibodies. Finally, we analyzed the limitations of EGFR monoclonal antibody therapy, and discussed the current strategies overcoming EGFR related drug resistance. This review will help us better understand the latest battles between EGFR monoclonal antibodies and resistant tumor cells, and the future directions to develop anti-tumor EGFR monoclonal antibodies with durable effects.

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“…Necitumumab is a recombinant human immunoglobulin G1 anti-EGFR mAb which prevents EGFR activation and downstream signalling by binding to it with high affinity. 6 The EGFR is crucial in cell survival, differentiation and proliferation, but its overexpression is related with tumour development. 7 Between 40% and 80% of patients with lung cancer have tumours with EGFR overexpression.…”

Section: Introductionmentioning

confidence: 99%

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

Ilić

Šipetić-Grujičić

Grujičić

et al. 2019

J Oncol Pharm Pract

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Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

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An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non–Small-Cell Lung Cancer

Cited by 17 publications

References 23 publications

First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis

First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis

The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

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