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Published on: April 22, 2019
Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in
Alice L Tang1, Thomas O'Neil1, Sean McDermott1
1Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Importance:
Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, is currently approved by the US Food and Drug Administration for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The potential neoadjuvant role of programmed cell death 1 inhibitors in primary surgical management of HNSCC and effects on surgical outcomes are poorly understood.
Objective:
To evaluate the incidence of postoperative adverse events in treatment-naive patients with advanced oral cavity cancer receiving neoadjuvant pembrolizumab when compared with matched controls, as part of a window-of-opportunity multi-institutional clinical trial assessing neoadjuvant pembrolizumab for locally advanced HNSCC.
Design, Setting, And Participants:
This retrospective cohort study at a single tertiary academic institution included treatment-naive patients with local regionally advanced oral cavity squamous cell carcinoma (OCSCC) who were undergoing surgical resection.
Exposures:
Patients with local regionally advanced resectable OCSCC who received neoadjuvant pembrolizumab were retrospectively reviewed for postoperative adverse events. Controls were matched by age, race, smoking status, and overall cancer stage based on historical data at the same institution. Matched-cohort analysis was performed using a McNemar test to assess differences between the groups.
Main Outcomes And Measures:
Incidence of adverse events following surgical resection of advanced OCSCC within 30 days of surgery and on continued follow-up.
Results:
A total of 64 patients (32 as part of the prospective clinical trial and 32 as controls; mean [SD] age, 59.6 [10.3] years; 28 [44%] women) were included in the analysis. Postoperative adverse events in the 32 patients receiving pembrolizumab included lymphedema (n = 20 [63%]), trismus (n = 7 [22%]), return to operating room (n = 7 [22%]), wound infection (n = 7 [22%]), fistula (n = 6 [19%]), wound dehiscence (n = 4 [13%]), flap failure (n = 3 [9%]), and hematoma (n = 2 [6%]). The matched control group demonstrated similar complication rates without considerable differences, except for trismus (n = 16 [50%]), which was greater by a difference of 28.1% (95% CI, 5.6%-50.6%) in the control group.
Conclusions And Relevance:
This cohort study examined surgical complications among patients with local regionally advanced OCSCC treated with neoadjuvant pembrolizumab and found that serious adverse events were similar to those in patients who underwent standard-of-care treatment. This suggests that there is no increased perioperative morbidity in the use of preoperative treatment with immunotherapy. Further prospective studies are needed to validate these findings for oral cavity cancer and other subsites of the head and neck.
Insights
Neoadjuvant pembrolizumab did not increase surgical complications in advanced oral cavity cancer patients. Postoperative adverse events were similar to standard care, suggesting immunotherapy is safe before surgery.
Area of Science:
- Oncology
- Immunotherapy
- Surgical Oncology
Background:
- Pembrolizumab is FDA-approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
- The neoadjuvant role of programmed cell death 1 (PD-1) inhibitors in HNSCC surgical management remains unclear.
- Understanding surgical outcomes after neoadjuvant PD-1 inhibition is crucial for treatment planning.
Purpose of the Study:
- To evaluate postoperative adverse events in treatment-naive advanced oral cavity cancer (OCSCC) patients receiving neoadjuvant pembrolizumab.
- To compare these events with matched controls undergoing standard surgical resection.
- To assess the safety of neoadjuvant immunotherapy in the perioperative setting.
Main Methods:
- Retrospective cohort study of treatment-naive OCSCC patients undergoing surgical resection.
- Comparison of patients receiving neoadjuvant pembrolizumab with matched historical controls.
- Matched-cohort analysis using McNemar test to compare postoperative adverse events within 30 days and on follow-up.
Main Results:
- 64 patients included (32 pembrolizumab, 32 controls).
- Pembrolizumab group experienced lymphedema (63%), trismus (22%), and wound infections (22%).
- Overall complication rates were similar between groups, with higher trismus incidence in controls (50% vs. 22%).
Conclusions:
- Neoadjuvant pembrolizumab in locally advanced OCSCC did not increase serious adverse events compared to standard care.
- Perioperative morbidity appears similar with or without neoadjuvant immunotherapy.
- Further prospective studies are warranted to confirm findings for OCSCC and other HNSCC subsites.
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