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
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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