KEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6090-TPS6090 ◽  
Author(s):  
Ravindra Uppaluri ◽  
Nancy Y. Lee ◽  
William Westra ◽  
Ezra E.W. Cohen ◽  
Robert I. Haddad ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Tumor ◽  
Locally Advanced ◽  
Pathological Response ◽  
Newly Diagnosed ◽  
Phase 3

TPS6090 Background: Evidence of efficacy and pathological response at the time of surgery was reported in two phase 2 studies (NCT02296684 and NCT02641093) of preoperative pembrolizumab in patients with high-risk, resectable, locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). The randomized, open-label, phase 3 KEYNOTE-689 trial ( NCT03765918) will evaluate efficacy and safety of pembrolizumab as neoadjuvant and adjuvant therapy in combination with SOC (radiotherapy ± cisplatin) in patients with previously untreated, resectable LA HNSCC. Methods: Patients with newly diagnosed LA HNSCC will be randomly assigned 1:1 to two treatment arms. Patients in arm A will receive neoadjuvant pembrolizumab (200 mg Q3W for two cycles) followed by surgical resection then SOC plus adjuvant pembrolizumab (15 cycles). Patients in arm B will undergo only surgical resection followed by adjuvant SOC. Eligibility criteria will include age ≥18 years; newly diagnosed, resectable, stage III/IVA HNSCC (AJCC Cancer Staging Manual, 8th edition); and ECOG performance status 0-1. Randomization will be stratified by primary tumor site (oropharynx/oral cavity vs larynx vs hypopharynx), tumor stage (III vs IVA), and HPV p16 status (oropharynx p16 positive vs oropharynx p16 negative or larynx/hypopharynx/oral cavity). Treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Patients in arm A will undergo the first radiologic imaging assessment after two cycles of neoadjuvant pembrolizumab and before surgery. In both arms, postoperative imaging will be performed 12 weeks after SOC, then every 3 months until the end of year 3, and then every 6 months until the end of year 5. Dual primary end points are major pathological response, defined as ≤10% invasive squamous cell carcinoma within resected primary tumor and sampled regional lymph nodes per blinded central pathology, and event-free survival. Secondary end points include overall survival, pathological complete response, and safety and tolerability. Recruitment is ongoing and will continue until ~600 patients are enrolled. Clinical trial information: NCT03765918.

Upfront chemotherapy and accelerated radiotherapy with EGFR inhibition for locally advanced inoperable head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6040-6040
Author(s):  
C. Mercke ◽  
G. Wickart-Johansson ◽  
H. Sjödin ◽  
G. Adell ◽  
J. Nyman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Stage Iv ◽  
Resected Specimen ◽  
Stage Iv Disease

6040 Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced head and neck squamous cell carcinoma. However, late toxicity is substantial.This phase II trial explores the feasibility and efficacy of combining neoadjuvant TPF and accelerated RT where the concomitant cytostatic component is replaced with cetuximab (E), a chimeric IgG1 mAb against EGFR. Methods: Patients (pts) had previously untreated stage III/IV M0,WHO 0–1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx and were scheduled for 2 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 day 1 and 5-FU 1,000 mg/m2 96 hours CI) every 3 weeks followed by RT (68 Gy/4.5 weeks) with E given one week before (400 mg/m2) and weekly during RT (250 mg/m2). A brachytherapy boost of 8 Gy was given to pts with oral cavity or oropharyngeal tumours. Neck dissection was planned for pts with N2–3 and complete response (CR) at the primary tumour. Tumour response was evaluated according to RECIST with CT, MRI or PET/CT after CT and at 6 weeks follow up. Toxicity (CTC 3.0) and quality of life (EORTC QLQ 30) was registered during and after treatment. Results: From 070401 to 081115 68 pts were enrolled, 56 had stage IV disease (T4, n = 14, N3, n = 9). Median age 57, 60 males, 3 oral cavity, 44 oropharynx, 10 larynx, and 11 hypopharynx. 30 pts were followed beyond 6 weeks and evaluated for response and early toxicity: stage IV disease 24 (T4, n = 6, N3, n = 3), median age 60, 25 males, 18 oropharynx, 5 larynx, and 7 hypopharynx. Remissions after TPF/after RT: CR 1/10, PR 15/18, SD 14/1, and PD 1. TPF as prescribed: 28/30 (pat refusal 1, renal insuff 1, dose reduction 0/28); E as prescribed: 22/30 (dermatitis 4, hypersensitivity 3, liver tox 1). Vital tumour in resected specimen 0/13. Alive at follow-up 29/30 (1 local failure). Conclusions: TPF followed by RT concomitant with E is feasible with manageable toxicities. Dermatitis in the irradiated neck, at least with the present accelerated fractionation, is troublesome to some patients but does not interrupt treatment and heals rapidly. To dispose of feeding tubes after disappearance of acute mucosal reactions has not been a problem. Early survival results are promising. Toxicity and survival results will be updated. [Table: see text]

Incidence of hypothyroidism in head and neck squamous cell carcinoma patients receiving radiotherapy with and without immune checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18551-e18551
Author(s):  
Jennifer Leddon ◽  
Martina Chirra ◽  
Arushi Agrawal ◽  
Logan Roof ◽  
Danny Trotier ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Tumor ◽  
Thyroid Dysfunction ◽  
Neck Squamous Cell Carcinoma

e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) involves a combination of surgery, chemotherapy, and radiotherapy (RT). RT for HNSCC is a known risk factor for the development of hypothyroidism. Recently, anti-PD1 therapies have been approved for recurrent and metastatic HNSCC and are moving to the forefront of HNSCC care. Similarly, thyroid dysfunction is a common immune-related adverse event following anti-PD1 therapy. Whether the addition of anti-PD1 to RT increases the likelihood of developing hypothyroidism remains unknown. Methods: The rate of hypothyroidism in HNSCC patients receiving RT (+/- chemotherapy and surgery) was compared to HNSCC patients receiving RT + anti-PD1 therapy either concurrently or after RT. Exclusion criteria were preexisting thyroid dysfunction, RT dose < 45 Gy and patients with incomplete treatment records. We defined clinical hypothyroidism as an elevation of TSH with low T3, T4 or elevation of TSH with symptoms requiring levothyroxine initiation. Hypothyroidism incidence was compared using Fisher’s exact test. Results: 153 patients were evaluated. In the RT group (N = 103), patients received RT +/- surgery or chemotherapy. 82/103 (80%) were male, median age was 57 and primary tumor groups included oropharynx 62/103 (60%), larynx 29/103 (28%), oral cavity 9/103 (9%) and other 3/103 (3%). In the RT + anti-PD1 group (N = 50), 36/50 (72%) were males, median age was 57 and primary tumor groups included oral cavity 19/50 (38%), oropharynx 17/50 (34%), larynx 8/50 (16%), and other 6/50 (12%). In the RT group, median follow up after RT was 801 days. In the RT+ anti-PD1 group, median follow up was 595 days from RT and 388 days from anti-PD1. The rate of hypothyroidism was significantly higher in the RT group 22.3% (23/103) versus 6% (3/50)after anti-PD1 therapy (p = 0.011). Multinomial logistical regression found no significant difference in hypothyroidism based on age, sex, or BMI. Larynx as primary tumor location was an independent risk factor for development of hypothyroidism (OR 4.74, p = 0.002). Conclusions: The addition of anti-PD1 therapy to standard HNSCC treatments does not significantly increase the risk of developing hypothyroidism. In fact, this study finds a lower incidence of hypothyroidism in HNSCC patient receiving RT + PD1 therapy which may be due to shorter duration of follow up and lower proportion of laryngeal cancer patients who are at relatively higher risk for surgical hypothyroidism.

scholarly journals A Prospective Observational Study on Treatment Evaluation in Patients Newly Diagnosed with Squamous Cell Carcinoma of Head and Neck in Bangladesh

2019 ◽  
Vol 10 (1) ◽  
pp. 17-22
Author(s):  
MA Hai ◽  
Ehteshamul Haque ◽  
Salim Reza ◽  
Mokhles Uddin ◽  
Kumkum Pervin
Keyword(s):  
Risk Factors ◽  
Squamous Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Routine Clinical Practice ◽  
Advanced Stage ◽  
Newly Diagnosed

Background: Most head and neck cancers are squamous cell carcinomas (SCCHN) that contribute to substantial morbidity and mortality worldwide. The disease is mostly diagnosed at locally advanced stage. Because treatment of head and neck cancers is complex and involves multiple modalities of surgery, radiotherapy and systemic therapy including chemotherapy and molecularly targeted agents; a multidisciplinary approach is needed. The study evaluated the current treatment approaches for patients newly diagnosed with SCCHN in Bangladesh. Methods: This prospective, observational and non-comparative, study enrolled eligible males and females of 18 years newly diagnosed with SCCHN at any stage of disease. No therapeutic intervention was implied rather selection of treatment strategy and dosage of therapy was on discretion of individual oncologist as per routine clinical practice. Results: A total of 64 patients with median age of 55 years were enrolled between August 2008 and July 2011. The majority of patients (42, 65.6%) were males. The major risk factors were betel leaf chewing along with jorda (smokeless tobacco) (62.5%) and cigarette smoking (32.8%), though most of the patients had multiple risk factors. No patient was diagnosed at early stage; all were in locally advanced disease at stage III (52, 81.3%) and IV (12, 18.8%). The oncologists prescribed neoadjuvant chemotherapy in half (32) of the patients, 19 (29.7%) patients received adjuvant chemotherapy and 13 (20.3%) received palliative chemotherapy. Only 3 (4.6%) of the patients received radiotherapy. Chemotherapy combination regimen included docetaxel, cisplatin and 5-fluorouracil (5-FU) and leucovorin was added to 2 patients. The dosage of chemotherapeutic agents was as per routine clinical practice of the oncologists. Neutropenia was the common hematological abnormality reported spontaneously in 16 (25%) patients. No serious adverse event was reported leading the patients to withdraw from therapy. During continuation of therapy 1 patient died due to sudden cardiac arrest who had medical history of previous myocardial infarction. Conclusion: This registry revealed that squamous cell carcinoma of head and neck region are mostly presented in advanced stage in Bangladesh and the majority of the patients are treated with combination chemotherapeutic regimens. Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 17-22

scholarly journals Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joris L. Vos ◽  
Joris B. W. Elbers ◽  
Oscar Krijgsman ◽  
Joleen J. H. Traets ◽  
Xiaohang Qiao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Primary Endpoint ◽  
Primary Tumor ◽  
Pathological Response ◽  
Neck Squamous Cell Carcinoma ◽  
Phase Ib ◽  
Neoadjuvant Immunotherapy

AbstractSurgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

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