Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC).

Abstract

6012 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.

MMP2 As An Independent Prognostic Stratifier In Oral Cavity Cancers

“…Immunotherapy is a new treatment modality, and its interest as neoadjuvant treatment is currently being evaluated (11), (12), (13). Numerous prognostic markers have been proposed for OCSCC, but none of them has shown independent validation, and translation to clinical practice (14).…”

Salvage surgery for squamous cell carcinoma of the head and neck in the era of immunotherapy: Is it time to clarify our guidelines?

“…Because immunotherapy has recently evolved in a relatively short time into a new standard for patients with advanced, incurable, heavily pretreated SCCHN, with 2 immune checkpoint inhibitors (ICPIs) approved in 2016, we believe that it is time to look at our long‐held practices in a new light . Historically, although induction chemotherapy has failed to produce significant improvements in patient survival, preoperative single doses of ICPIs have produced impressive responses with little toxicity in different tumor types, including SCCHN . Chemoresponders consistently show improved survival and increased responses to subsequent radiation.…”

The evolving role of immuno‐oncology for the treatment of head and neck cancer

“…In patients with HPV+ and HPV‐ resectable SCCHN, preoperative administration of nivolumab mediated a reduction in tumor size in approximately 50% of patients . Similar findings were also reported using the anti–PD‐1 mAb pembrolizumab, suggesting that these results are not secondary to a use of a particular drug . While we as a field continue to await more mature results, the high response rates associated with PD‐L1:PD‐1 blockade in the neoadjuvant setting, hold tremendous promise for patients presenting with advanced SCCHN—particularly those who are HPV negative .…”

“…111 Similar findings were also reported using the anti-PD-1 mAb pembrolizumab, suggesting that these results are not secondary to a use of a particular drug. 112 While we as a field continue to await more mature results, the high response rates associated with PD-L1: PD-1 blockade in the neoadjuvant setting, hold tremendous promise for patients presenting with advanced SCCHN-particularly those who are HPV negative. 113 Of equal import, as previously mentioned, these window of opportunity trials are also an excellent means to get an early indication of how/whether new I-O targets are worth resource investment.…”