Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR

Basavaraj, Chetana; Sierra, Patricia; Shivu, Jatteppanavar; Melarkode, Ramakrishnan; Montero, Enrique; Nair, Pradip

doi:10.4161/cbt.10.7.12793

Cited by 60 publications

(49 citation statements)

References 42 publications

(49 reference statements)

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“…In HNSCC, EGFR was overexpressed in 70-90% of the patients and KRAS mutations were also rarely found, which may represent a good response to anti-EGFR mAbs [8][9][10]. The characteristics of EGFR-RAS-RAF signaling pathway molecules of the penile SCC found in our previous study were similar to those of HNSCC [4].…”

Section: Discussionsupporting

confidence: 57%

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

Men

Gou²,

Qiu³

et al. 2014

Anti-Cancer Drugs

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Our previous study showed that the features of epidermal growth factor receptor (EGFR)-RAS signaling in penile squamous cell carcinoma (SCC) suggested potential benefits of anti-EGFR monoclonal antibodies (mAbs) for penile SCC. Here, we report, for the first time, a combination of nimotuzumab (an EGFR mAb) with chemotherapy that resulted in a partial response in a 44-year-old patient with penile SCC, who developed bilateral inguinal node metastasis after primary partial penile amputation. The literature of case reports of anti-EGFR mAbs in penile SCC was also reviewed.

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Section: Discussionsupporting

confidence: 57%

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

Men

Gou²,

Qiu³

et al. 2014

Anti-Cancer Drugs

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“…Nimotuzumab has demonstrated efficacy characterized by the induction of a long-term stable disease with a very low toxicity profile in patients with head and neck squamous cell carcinoma, 28,30 pancreatic cancer, 31 non-small cell lung cancer 32 and glioblastoma. [33][34][35] No studies with nimotuzumab have been reported in cervical cancer; however, currently nimotuzumab is being studied in different treatment settings of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer

Cetina¹,

Crombet

Jiménez-Lima

et al. 2015

Cancer Biology & Therapy

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Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second-or thirdline chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m 2 as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m 2 ) or cisplatin (50 mg/m 2 ) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.

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“…Nimotuzumab is a fully humanized IgG1 mAb specific to the extracellular domain of EGFR. Preliminary data from a phase II trial in locally advanced HNSCC, evaluating (chemo) radiation with or without nimotuzumab, suggested a correlation between EGFR expression and survival benefit [56]. In a biomarker-modulation study, 9 of 10 patients with unresectable HNSCC achieved objective responses to nimotuzumabradiotherapy [57].…”

Section: Promising Immunotherapiesmentioning

confidence: 99%

Promising systemic immunotherapies in head and neck squamous cell carcinoma

2013

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SUMMARY Patients with head and neck squamous cell carcinoma (HNSCC) demonstrate poor survival and significant treatment morbidity with standard therapy. The immune profile in HNSCC, whether caused by carcinogen exposure or human papillomavirus (HPV), is notably immunosuppressive. Early clinical trials of immunotherapy in HNSCC were troubled by systemic toxicity or difficulties in local administration. Now, interest in immunotherapy has been revitalized by mechanistic insights into immune evasion by HNSCC, coupled to ongoing development of novel immunotherapies. This review will summarize immune escape mechanisms in HNSCC, namely downregulation of tumor antigen (TA) presentation, aberrant regulation of the signal transducer and activator of transcription (STAT) family, the immunosuppressive cytokine milieu, and dysregulation of immune effector cells. Therapeutic strategies hypothesized to specifically counter HNSCC immunosuppression will then be discussed. We will survey TA-targeted monoclonal antibodies (mAb), including the prototype cetuximab, as well as adjunctive strategies to enhance antibody-dependent cell-mediated cytotoxicity. We will review immunomodulation to restore STAT1/STAT3 activation balance. Examples of mAb therapy to block immunosuppressive cytokines, such as interleukin-6 or VEGF, will be provided. mAbs which release co-inhibitory T cell receptors such as CTLA-4 and PD-1, overexpressed in HNSCC, also hold therapeutic promise. Finally, we will describe principles for therapeutic vaccination in HPV-associated HNSCC, where non-host TAs such as viral oncoproteins represent ideal targets, and HPV-negative HNSCC, where p53 is a promising target. Insights into immunosuppression in HNSCC have elucidated mechanistic targets for immunotherapy. Rational clinical investigation may lead to effective stand alone or combinatorial treatment approaches.

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Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR

Cited by 60 publications

References 42 publications

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer

Promising systemic immunotherapies in head and neck squamous cell carcinoma

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