Dataset Information

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

ABSTRACT:

Purpose

Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.

Patients and methods

Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684).

Results

Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.

Conclusions

Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

SUBMITTER: Uppaluri R

PROVIDER: S-EPMC7547532 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

Uppaluri Ravindra R Campbell Katie M KM Egloff Ann Marie AM Zolkind Paul P Skidmore Zachary L ZL Nussenbaum Brian B Paniello Randal C RC Rich Jason T JT Jackson Ryan R Pipkorn Patrik P Michel Loren S LS Ley Jessica J Oppelt Peter P Dunn Gavin P GP Barnell Erica K EK Spies Nicholas C NC Lin Tianxiang T Li Tiantian T Mulder David T DT Hanna Youstina Y Cirlan Iulia I Pugh Trevor J TJ Mudianto Tenny T Riley Rachel R Zhou Liye L Jo Vickie Y VY Stachler Matthew D MD Hanna Glenn J GJ Kass Jason J Haddad Robert R Schoenfeld Jonathan D JD Gjini Evisa E Lako Ana A Thorstad Wade W Gay Hiram A HA Daly Mackenzie M Rodig Scott J SJ Hagemann Ian S IS Kallogjeri Dorina D Piccirillo Jay F JF Chernock Rebecca D RD Griffith Malachi M Griffith Obi L OL Adkins Douglas R DR

Clinical cancer research : an official journal of the American Association for Cancer Research 20200714 19

<h4>Purpose</h4>Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.<h4>Patients and methods</h4>Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postopera ...[more]

PMID: 32665297

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Dataset Information

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

Purpose

Patients and methods

Results

Conclusions

Publications

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

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