Necitumumab 800mg/50ml solution for infusion vials

BACKGROUND: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM). MATERIALS AND METHODS: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints. RESULTS: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity. CONCLUSIONS: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.

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dermatoses observed in adults with systemic diseases [1].While the categorisation provided by Rapini in 1989 has been widely adopted, it is important to note that the classification of PD remains a topic requiring further investigation and unification.PD comprises a rare group of diseases most often associated with kidney disease, diabetes, and metabolic syndrome in patients, but there are also reports of PD induced by drugs.We are the first to perform a literature review to summarise PD caused by molecularly targeted therapy (MTT) drugs (sorafenib, nilotinib, dasatinib, erlotinib, gefitinib, vemurafenib, lenvatinib, sirolimus, bevacizumab, necitumumab, panitumumab, cetuximab, terepril, bendamustine-rituximab). MTT drugs are one of the major modalities of medical treatment for cancer, which block the growth of cancer cells by AbstrActPerforating dermatoses represents a diverse group of skin diseases characterised by extrusion of dermal materials through the skin.Perforating dermatoses are grouped according to the types of eliminated material and clinical features into the following: reactive perforating collagenosis, elastosis perforans serpiginous, perforating folliculitis, and Kyrle's disease.We conducted a literature review to investigate the associations between perforating dermatoses and drugs.Perforating dermatoses can be induced by the molecularly targeted therapy drugs (sorafenib, nilotinib, dasatinib, erlotinib, gefitinib, vemurafenib, lenvatinib, sirolimus, bevacizumab, necitumumab, panitumumab, cetuximab, bendamustine-rituximab, terepril), monoclonal antibodies (infliximab, etanercept, ranibizumab, natalizumab), as well as immunomodulatory imide drugs (lenalidomide, leflunomide), antiretroviral drugs (indinavir, telaprevir) and penicillamine.Sorafenib is the most common molecularly targeted therapy drug which was described as a cause of perforating dermatoses.The mechanisms responsible for inducing perforating dermatoses with drugs are unknown.

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The treatment options for metastatic non-small-cell lung cancer (NSCLC) have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR), when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs) of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations. Monoclonal antibodies have also been developed that block the EGFR at the cell surface and work in conjunction with chemotherapy. Necitumumab is a second-generation fully human IgG1 monoclonal antibody that has shown promise in metastatic NSCLC. The benefit has mostly been restricted to squamous cell lung cancer in the frontline setting. Considering that the survival advantage for these patients was modest, there is a need to discover biomarkers that will predict which patients will likely have the best outcomes. This review focuses on the development and clinical trial experience with necitumumab in NSCLC.

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BACKGROUND: Platinum-based combination therapy plus a programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitor is a standard treatment for patients with stage IV non-small cell lung cancer. However, necitumumab is used with gemcitabine and cisplatin as a first-line treatment option for squamous cell lung cancer (SqCLC). Furthermore, the combination of necitumumab with immune checkpoint inhibitors has the potential to enhance tumor immunity and improve the therapeutic effect. Thus, we planned and initiated this phase I/II study to evaluate the safety and efficacy of necitumumab plus pembrolizumab, nanoparticle albumin-bound (nab)-paclitaxel), and carboplatin therapy for patients with previously untreated SqCLC. PATIENTS AND METHODS: In phase I, the primary endpoint is the tolerability and recommended dose of necitumumab combined with pembrolizumab plus nab-paclitaxel and carboplatin. In phase II, the primary endpoint is the overall response rate. Secondary endpoints are disease control rate, progression-free survival, overall survival, and safety. Forty-two patients will be enrolled in phase II. CONCLUSION: This is the first study to investigate the efficacy and safety of necitumumab plus pembrolizumab combined with platinum-based chemotherapy in patients with previously untreated SqCLC.

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Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear. Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations ( p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively ( p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated ( r = 0.389, p &lt; 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN ( n = 12) had significantly poorer progression-free survival (PFS) than those without the condition ( n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021). Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival.

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