2017 ASCO Annual Meeting!
Session: What's Next in Immunotherapy for Head and Neck Cancer?
Type: Clinical Science Symposium
Time: Tuesday June 6, 8:00 AM to 9:30 AM
Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC).
Head and Neck Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 6012)
Author(s): Ravindra Uppaluri, Paul Zolkind, Tianxiang Lin, Brian Nussenbaum, Ryan S Jackson, Jason Rich, Patrik Pipkorn, Randal Paniello, Wade Thorstad, Loren Michel, Tenny Mudianto, Peter John Oppelt, Tanya Marya Wildes, Gavin P Dunn, Jay F Piccirillo, Dorina Kallogjeri, Scott Rodig, Ian S. Hagemann, Rebecca Chernock, Douglas Adkins; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA; Washington University School of Medicine in St. Louis, St. Louis, MO; Washington University in St. Louis, St. Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Department of Pathology and Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA; Washington University School of Medicine in St. Louis and Siteman Cancer Center, St. Louis, MO
Background: Pembrolizumab has efficacy in metastatic HNSCC. We hypothesized that treatment intensification in surgically resectable HPV-negative, Stage III/IV HNSCC with neoadjuvant plus post-operative adjuvant (POA) pembrolizumab would be safe and reduce 1-year locoregional recurrence/distant metastases (LRR/DM) from 35% (historical: Cooper and Bernier NEJM 2004) to 15%. Methods: Phase II trial where all eligible patients received 1 dose of pembrolizumab (200 mg) prior to surgery and only those with high-risk pathologic features (HRPF: extracapsular extension/positive margin) were given POA cisplatin and radiation followed by pembrolizumab. PD-L1 staining was assessed by immunohistochemistry (9A11 antibody). Results: The study continues to enroll. Characteristics of 21 enrolled patients (pts) were median age 59 (32-87) yrs, tobacco use 81% (17 pts), clinical T2 (n = 2), T3 (n = 1), T4 (n = 18), and cN0/1 (n = 8), cN2 (n = 13). Preliminary analyses revealed five important findings: 1) No serious study drug-related AEs or unexpected surgical delays/complications, 2) No LRR/DM events in the first 10 patients with > 1-year follow-up after surgery 3) HRPF rate of 38% (95% CI: 18%-62%) (expected: 80%), 4) 43% of pts (95% CI: 22%-66%) with pathologic treatment response to neoadjuvant pembrolizumab (definition: tumor necrosis and/or giant cell/histiocytic reaction to keratinous debris in > 10% of tumor area), and 5) 48% of pts (95% CI:26%-70%) with clinical-to-pathologic downstaging. Pathologic treatment effect (TE) in ≥ 70% of the resected tumor or lymph node tissue area occurred in 6/21 pts (29%). Baseline tumor biopsies were PD-L1 positive ( > 1% of tumor cells) in 11/19 (58%) evaluable samples and in 7/8 (88%) evaluable pathologic responders. A significant correlation existed between baseline PD-L1 expression on tumor cells and pathologic treatment effect in the tumor (correlation coefficient: 0.72 and p = 0.0005). Conclusions: Neoadjuvant and adjuvant pembrolizumab was safe and well tolerated. We observed several lines of evidence supporting an anti-tumor effect in these pts with a single dose of pre-operative pembrolizumab. Further evaluation of this strategy is warranted. Clinical trial information: NCT02296684