Clinical Activity and Safety of Medi4736, an Anti-Pd-L1 Antibody, in Patients with Head and Neck Cancer

Fury, Matthew G.; Ou, Sai‐Hong Ignatius; Balmanoukian, Ani Sarkis; Hansen, Ann; Massarelli, Erminia; Blake-Haskins, Andy; Li, X.; Robbins, Paul B.; Vasselli, Jim; Segal, Neil H.

doi:10.1093/annonc/mdu340.3

Cited by 25 publications

(17 citation statements)

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“…A phase III trial of anti-PD-1 nivolumab versus investigator's choice therapy is ongoing in platinum-refractory metastatic/ recurrent HPV-related and unrelated HNSCC and a similarly designed trial is planned with pembrolizumab ( Table 2). The response rate to anti-PD-L1 MEDI4736 was surprisingly lower in HPV þ OPC (4%, 1 of 23), compared with HPV À HNSCC (19%, 4 of 21) in an expansion cohort of a phase I/II trial (42). Accrual continues in this cohort to determine the difference in overall response rate (ORR) based on HPV status.…”

Section: Reversing Immune Evasionmentioning

confidence: 97%

New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic

Massarelli

Ferrarotto

Glisson

2015

Clinical Cancer Research

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The past two decades have been witness to a steadily increasing incidence of oropharynx cancer, specifically related to human papillomavirus (HPV), primarily affecting middle-aged Caucasian men, in North America and Europe. The ever-increasing incidence, now clearly an epidemic, of this unique clinicopathologic entity demands new perspectives in diagnosis and staging and presents unique challenges in clinical research, given the excellent prognosis afforded by chemoradiation for the majority of these patients. To reduce the morbidity of late toxicity in survivors without compromising the high rates of survival currently enjoyed, and simultaneously address the poor prognosis of those with recurrence, it is critical to capitalize on the viral etiology and translate discoveries in genomics, target/drug discovery, viral oncogenesis, and immunbiology to improved outcomes for patients. Herein, we review ongoing and planned clinical research for HPV-related oropharynx cancer, the basis for which is constituted by prior clinical observations, knowledge of the genomic alterations and altered biology associated with HPV-related oncogenesis, and hope that molecularly targeted and immunomodulatory therapies can be harnessed. Clin Cancer Res; 21(17); 3821-8. Ó2015 AACR. Disclosure of Potential Conflicts of Interest Editor's DisclosuresThe following editor(s) reported relevant financial relationships: J.L. Abbruzzese is a consultant/advisory board member for Celgene and Halozyme. Learning ObjectivesUpon completion of this activity, the participant should have increased knowledge regarding the epidemiology and clinical presentation of HPV-related oropharynx cancer, understand the rationale for deintensification and be familiar with clinical research strategies to reduce late effects in curative-intent treatment, and be aware of the biologic rationale for strategies targeting the immune system and molecular alterations in treatment of relapsed and refractory cancer.

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Section: Reversing Immune Evasionmentioning

confidence: 97%

New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic

Massarelli

Ferrarotto

Glisson

2015

Clinical Cancer Research

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“…The study was terminated early after an independent monitoring panel determined the primary endpoint of improvement in OS was met with nivolumab. Another promising anti PD-L1 antibody is durvalumab (MEDI4736), which has shown promising results (∼14% response rate as per RECIST criteria, with 24% response rate in PD-L1+ patients) in a phase I trial (74). A phase III trial evaluating durvalumab alone or in conjunction with tremelimumab compared to standard treatment is under way in patients with advanced HNSCC (NCT02369874).…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications.

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“…There is currently an ongoing phase I/II multicenter, open‐label trial (NCT01693562) examining the efficacy and safety of an anti‐PD‐L1 monoclonal antibody (MEDI4736) in blocking T‐cell downregulation in patients with SCC of the head and neck. Interim data suggest that MEDI4736 has an adequate safety profile and can generate partial responses and/or halting of disease progression …”

Section: Elective Nodal Dissection Of the Head And Neckmentioning

confidence: 99%

Review of high‐risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology

et al. 2016

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Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network (NCCN ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017.

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Clinical Activity and Safety of Medi4736, an Anti-Pd-L1 Antibody, in Patients with Head and Neck Cancer

Cited by 25 publications

References 0 publications

New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic

New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Review of high‐risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology

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