Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: Rationale for future randomised trials in human papilloma virus-negative disease

Harrington, Kevin; Berrier, A.; Robinson, Martin; Remenár, Éva; Housset, M.; Mendoza, Fernando Hurtado de; Fayette, Jérôme; Mehanna, Hisham; El‐Hariry, Iman; Compton, Natalie; Franklin, Natalie; Biswas-Baldwin, Nigel; Lau, Mike; Legenne, Philippe; Kumar, Rejnish

doi:10.1016/j.ejca.2012.11.023

Cited by 103 publications

(46 citation statements)

References 11 publications

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“…Recently, Harrington et al [89] reported a phase II study assessing the activity and safety of concurrent CRT and lapatinib followed by maintenance treatment. Interestingly, no difference in PFS between HPV-positive patients treated with lapatinib and placebo was observed.…”

Section: Recurrent or Metastatic Hnsccmentioning

confidence: 99%

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Denaro¹,

Russi

Adamo

et al. 2014

Oncology

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer death worldwide. Its treatment is complex and evolving. In general, early-stage disease may be managed with single-modality treatment while an advanced stage (about 60% of clinical presentation) needs a multidisciplinary approach. In this setting concurrent chemoradiation has been associated with improvement in locoregional control and organ preservation, but at the cost of significant acute and chronic toxicity. Molecular target therapies specially directed to epidermal growth factor receptor (EGFR) might improve the outcomes and reduce toxicities. In recurrent-metastatic (R/M) HNSCC, cetuximab, a monoclonal antibody against EGFR, plus platinum-based chemotherapy (CT) allow an overall survival (OS) of about 10 months. However, the prognosis for R/M-HNSCC remains dismal and additional efforts are needed. At the 2013 American Society of Clinical Oncology (ASCO) Meeting, data on induction CT, anti-EGFR inhibitors, innovative molecular targets and predictor factors were reported. Further results on target therapies were presented at the European Cancer Congress (ECC) 2013, where a large study also showed that hyperfractionated radiotherapy (RT) improve OS rates compared with standard RT. The aim of this review is to discuss current standards and emerging therapies by considering recent new updates.

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Section: Recurrent or Metastatic Hnsccmentioning

confidence: 99%

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Denaro¹,

Russi

Adamo

et al. 2014

Oncology

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“…Rather, these data suggest that targeting EGFR alone is probably not sufficient, especially in a ligand rich environment of advanced disease, and that patient population selection is important (Harrington et al, 2013;Wilson et al, 2011). For example, although lapatinib, a dual TKI of both EGFR and HER2, was not effective either as a monotherapy in R/M SCCHN (de Souza et al, 2012) or as an adjuvant therapy for postsurgical patients with high risk (Harrington et al, 2014), it did demonstrate promise in HPV (human papillomavirus) negative treatment naive patients with unresectable stage III/IVA-B SCCHN (Harrington et al, 2013) -based on which, lapatinib is currently being evaluated in HPV negative SCCHN in combination with CCRT (concurrent chemoradiation therapy) (RTOG 3501). Similarly, afatinib, a TKI for pan-HER members, was recently shown in a phase II study to be able to achieve comparable disease control rate (50%) to cetuximab (56.5%) in R/M SCCHN whose disease has progressed after platinum-containing therapy (Seiwert et al, 2014).…”

Section: Egfr and Its Role In Hncmentioning

confidence: 91%

Targeting HER (ERBB) signaling in head and neck cancer: An essential update

Zhang

Saba

Chen

et al. 2015

Molecular Aspects of Medicine

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HNC (head and neck cancer) remains the 6th most common carcinoma worldwide. The suboptimal survival and toxicities observed with conventional approaches warrant exploration of novel therapeutic strategies such as targeted therapies. Although targeting EGFR (epidermal growth factor receptor) with cetuximab demonstrated clinical promise, HER (human epidermal growth factor receptor) or ERBB (erythroblastic leukemia viral oncogene homolog) targeted therapy in HNC has overall been suboptimal to date in clinical settings. Overcoming the resistance as well as identifying new strategies therefore remains a significant challenge. In this review, we will discuss the emerging roles of HER members besides EGFR. A comprehensive "three-dimensional" view of HER signaling pathway from the importance of EGFR nuclear translocation to our maturing concept of receptors' "spatial regulation", as well as the interdependence and interaction among different HER members will also be addressed to complete an essential update of HER signaling in HNC.

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“…Lapatinib has dual specificity for EGFR and HER2 and is in use in breast cancer. In HNSCC trials, it has shown activity in p16-negative tumours in combination with chemoradiation, 47 and is currently being evaluated in the recurrent/metastatic setting in combination with capecitabine chemotherapy (NCT01044433), and in a phase III adjuvant trial (NCT 00424255). Afatinib irreversibly blocks EGFR, HER2 and ErbB4 and is being investigated in the recurrent/metastatic, neoadjuvant and adjuvant settings (NCT 01856478, NCT01538381 and NCT01345669).…”

Section: Epidermal Growth Factor Receptor (Egfr) Pathwaymentioning

confidence: 99%

Clinical update on cancer: molecular oncology of head and neck cancer

et al. 2014

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Head and neck cancers encompass a heterogeneous group of tumours that, in general, are biologically aggressive in nature. These cancers remain difficult to treat and treatment can cause severe, long-term side effects. For patients who are not cured by surgery and/or (chemo)radiotherapy, there are few effective treatment options. Targeted therapies and predictive biomarkers are urgently needed in order to improve the management and minimise the treatment toxicity, and to allow selection of patients who are likely to benefit from both nonselective and targeted therapies. This clinical update aims to provide an insight into the current understanding of the molecular pathogenesis of the disease, and explores the novel therapies under development and in clinical trials.

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Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: Rationale for future randomised trials in human papilloma virus-negative disease

Cited by 103 publications

References 11 publications

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Targeting HER (ERBB) signaling in head and neck cancer: An essential update

Clinical update on cancer: molecular oncology of head and neck cancer

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