Correction: Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–unrelated Head and Neck Cancer: A Multicenter, Phase II Trial

Uppaluri, Ravindra; Campbell, Katie M.; Egloff, Ann Marie; Zolkind, Paul; Skidmore, Zachary L.; Nussenbaum, Brian; Paniello, Randal C.; Rich, Jason T.; Jackson, Ryan; Pipkorn, Patrik; Michel, Loren S.; Ley, Jessica; Oppelt, Peter; Dunn, Gavin P.; Barnell, Erica K.; Spies, Nicholas C.; Lin, Tianxiang; Li, Tiantian; Mulder, David T.; Hanna, Youstina; Cirlan, Iulia; Pugh, Trevor J.; Mudianto, Tenny; Riley, Rachel; Zhou, Liye; Jo, Vickie Y.; Stachler, Matthew D.; Hanna, Glenn J.; Kass, Jason; Haddad, Robert I.; Schoenfeld, Jonathan D.; Gjini, Evisa; Lako, Ana; Thorstad, Wade L.; Gay, Hiram A.; Daly, Mackenzie; Rodig, Scott J.; Hagemann, Ian S.; Kallogjeri, Dorina; Piccirillo, Jay F.; Chernock, Rebecca D.; Griffith, Malachi; Griffith, Obi L.; Adkins, Douglas R.

doi:10.1158/1078-0432.ccr-20-4484

Cited by 7 publications

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“…All patients received 200 mg neoadjuvant Pembrolizumab and only patients with high-risk pathology (positive margins and/or extranodal extension) received 200 mg adjuvant Pembrolizumab every three weeks for six cycles. The one-year relapse rate among patients with high-risk pathology was only 16.7% ( 11 , 12 ). Tumour necrosis rates greater than 50% as in our case occurred in 22% of patients and treatment response with ≥10% necrotic tumour cells correlated significantly with initial tumour PD-L1 expression as well as CD8+ cytotoxic T-cell invasion ( 11 , 12 ).…”

Section: Discussionmentioning

confidence: 96%

“…The one-year relapse rate among patients with high-risk pathology was only 16.7% (11,12). Tumour necrosis rates greater than 50% as in our case occurred in 22% of patients and treatment response with ≥10% necrotic tumour cells correlated significantly with initial tumour PD-L1 expression as well as CD8+ cytotoxic T-cell invasion (11,12). Another ongoing randomized, open-label phase 3 trial called Keynote-689 (NCT03765918) is similarly evaluating the effect of pre-and postoperative use of Pembrolizumab in addition to surgery and standard chemoradiation in patients with previously untreated, resectable, and locally advanced HNSCC (30).…”

Section: Discussionmentioning

confidence: 98%

“…Hence, we suggest that neoadjuvant use of PD-1 inhibitors should be further investigated to increase therapeutic efficacy and expand the collective of patients with favourable response to immunotherapy. In a recently published multicentre phase II study, Uppaluri et al reported the successful neoadjuvant use of Pembrolizumab in addition to standard therapy in patients with locally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) (11,12). All patients received 200 mg neoadjuvant Pembrolizumab and only patients with high-risk pathology (positive margins and/or extranodal extension) received 200 mg adjuvant Pembrolizumab every three weeks for six cycles.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the clinical situation and unfavourable prognosis, all therapeutic options were discussed with the patient. Additional to the current standard of care and based on recently published results on the administration of Pembrolizumab prior to surgical therapy ( 11 , 12 ), the possibility of neoadjuvant and adjuvant immunotherapy as an individual healing attempt was discussed. The patient was informed in detail about the experimental nature of such treatment and the possible risks, including fatal autoimmunologic side effects.…”

Section: Case Descriptionmentioning

confidence: 99%

“…Neoadjuvant immunotherapeutic treatment of OSCC is currently not approved in the EU and US but is under intense investigation in large clinical trials (NCT02296684, NCT02641093 and NCT03765918). A recently published Phase 2 trial characterized neoadjuvant administration of Pembrolizumab 200 mg 2-3 weeks prior to surgery as safe and reported pathological response in 44% of patients with 0% pathologic complete response ( 11 , 12 ). As of late it was discovered that tumours present their driver mutations more poorly on specific MHC molecules in younger and female than in older and male patients ( 6 ), showing evidence that presentation of tumour driver mutations varies with sex and age.…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

et al. 2021

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BackgroundThe treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient’s prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy.Case PresentationWe describe the case of a woman in her late 30’s who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence.ConclusionsThe case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.

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