A Phase Ib Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Human Papiilloma Virus (Hpv)-Positive and Negative Head and Neck Cancer (Hnc)

Chow, Laura Q.; Burtness, Barbara; Weiss, Jared; Berger, Raanan; Eder, Joseph P.; Gonzalez, Edward J.; Pulini, Jennifer; Johnson, Jeffrey; Dolled‐Filhart, Marisa; Emancipator, Kenneth; Lunceford, Jared; Pathiraja, Kumudu; Gause, Christine K.; Cheng, Jonathan D.; Seiwert, Tanguy Y.

doi:10.1093/annonc/mdu438.32

Cited by 34 publications

(22 citation statements)

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“…The ORR of these agents ranges from 20 to 50% depending on the agent used and expression of PD-L1. Like in other malignancies, these agents are well tolerated and provide a much needed option for a disease with very few treatments outside of chemotherapy (Chow et al, 2014). Given the success of these agents in the metastatic setting, future trials will address the use of these agents in earlier settings such as the neo-adjuvant, adjuvant, and possibly as primary treatments for patients with intact bladders.…”

Section: Discussionmentioning

confidence: 99%

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Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy

Swaika

Hammond

Joseph

2015

Molecular Immunology

188

155

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Section: Discussionmentioning

confidence: 99%

“…There was a positive association between PD-L1 express and both ORR and PFS. Grade 3 or above toxicity was seen in 17% of the participating patients (Chow et al, 2014).…”

Section: Clinical Datamentioning

confidence: 96%

Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy

Swaika

Hammond

Joseph

2015

Molecular Immunology

188

155

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“…Responses were similar between HPV-positive and HPV-negative patients, although denser PDL1 expressing tumors showed a higher ORR of 50%. 67 In an expansion cohort included in the KEYNOTE-012 trial, 132 patients with HNSCC regardless of PDL1 expression and HPV status were treated, with the pembrolizumab dosage decreased to 200 mg every 3 weeks. 68 The ORR was 25% in 117 patients with evaluable tumor, with 56% of patients having a decrease in tumor burden.…”

Section: Other Trials Of Pembrolizumab As a Single Agentmentioning

confidence: 99%

Pembrolizumab (Keytruda)

Kwok

Yau

Chiu

et al. 2016

Human Vaccines & Immunotherapeutics

324

224

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The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.

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“…Recently, pembrolizumab showed promising activity in gastric [45], urothelial [46], head and neck [47], and nonsmall cell lung (NSCLC) [48] cancers and is now being investigated in several trials alone or in combination with other drugs (Tables 2 and 3). …”

Section: Clinical Experience With Anti-pd-1 Antibodiesmentioning

confidence: 99%