Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase 2 Trial
Autor: | Ryan S. Jackson, Mackenzie Daly, Jason I. Kass, Tiantian Li, Evisa Gjini, Youstina Hanna, Ian S. Hagemann, Liye Zhou, Douglas Adkins, Trevor J. Pugh, Gavin P. Dunn, Jessica Ley, Wade L. Thorstad, Glenn J. Hanna, Scott J. Rodig, Rachel S. Riley, Randal C. Paniello, Malachi Griffith, David Mulder, Tianxiang Lin, Ana Lako, Nicholas C. Spies, Matthew D. Stachler, Jason T. Rich, Rebecca D. Chernock, Loren S. Michel, Ravindra Uppaluri, Dorina Kallogjeri, Patrik Pipkorn, Robert I. Haddad, Vickie Y. Jo, Brian Nussenbaum, Jonathan D. Schoenfeld, Iulia Cirlan, Jay F. Piccirillo, Peter Oppelt, Paul Zolkind, Ann Marie Egloff, Obi L. Griffith, Zachary L. Skidmore, Erica K. Barnell, Tenny Mudianto, Katie M. Campbell |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Oncology Cancer Research medicine.medical_treatment Pembrolizumab B7-H1 Antigen 0302 clinical medicine Monoclonal 80 and over Lymphocytes Papillomaviridae Humanized Adjuvant Cancer Aged 80 and over 0303 health sciences Middle Aged Primary tumor Neoadjuvant Therapy 3. Good health Infectious Diseases Local Chemotherapy Adjuvant 030220 oncology & carcinogenesis Female Patient Safety Adult medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Oncology and Carcinogenesis Locally advanced Antibodies Monoclonal Humanized Article Antibodies Interferon-gamma 03 medical and health sciences Lymphocytes Tumor-Infiltrating Rare Diseases Clinical Research Internal medicine medicine Carcinoma Humans Chemotherapy Tumor-Infiltrating Oncology & Carcinogenesis Dental/Oral and Craniofacial Disease Adverse effect Histiocyte Aged 030304 developmental biology Squamous Cell Carcinoma of Head and Neck business.industry Head and neck cancer medicine.disease Confidence interval 030104 developmental biology Neoplasm Recurrence Giant cell Sexually Transmitted Infections Neoplasm Recurrence Local business |
Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research, vol 26, iss 19 Clin Cancer Res Int J Radiat Oncol Biol Phys |
Popis: | SUMMARYBackgroundPembrolizumab improved survival of patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this phase 2 trial were to determine if pembrolizumab administered to patients with resectable locally advanced, human papillomavirus (HPV)-unrelated HNSCC would be safe, result in pathologic tumor response (pTR), and lower the relapse rate.MethodsNeoadjuvant pembrolizumab (200 mg) was administered 2-3 weeks before surgery. Resection of the primary tumor and involved/at-risk nodes was performed. Post-operative (chemo) radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) were to receive adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (NCT02296684), and is ongoing but closed to accrual.FindingsBetween June 30, 2015, and March 30, 2018, 36 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%). pTR ≥10% correlated with baseline tumor PD-L1 expression, immune infiltrate, and IFN-γ pathway activity. Matched sample analysis showed compensatory upregulation of multiple immune inhibitory checkpoints in patients with pTR-0, and confirmed that clonal loss occurred in some patients. The one-year relapse rate among the eighteen patients with high-risk pathology was 16.7% (95%CI: 3.6-41.4%).ConclusionsAmong patients with locally advanced, HPV-unrelated HNSCC, neoadjuvant pembrolizumab was safe, and resulted in pTR-1 or pTR-2 in 44% of patients. The one-year relapse rate in patients with high-risk-pathology was lower than historical.FundingMerck, NCI, NIDCR, NHGRI and The V Foundation. |
Databáze: | OpenAIRE |
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