summary
GRADE
treatment
patients
risk of bias
overview
DCR deaths (OS) deaths (OS) (extension) DOR objective responses (ORR) objective responses (ORR) (extension) PFS (extension) progression or deaths (PFS) AE (any grade) AE (grade 3-4) AE (grade 3-5) AE leading to death (grade 5) AE leading to treatment discontinuation (any grade) SAE (any grade) STRAE (any grade) TRAE (any grade) TRAE (grade 3-4) TRAE leading to death (grade 5) TRAE leading to discontinuation (any grade) TRAE leading to discontinuation (grade 3-4) Abdominal pain TRAE (grade 3-4) Acute kidney injury TRAE (grade 3-4) Adrenal insufficiency TRAE (grade 3-4) Alopecia TRAE (grade 3-4) Anaemia TRAE (grade 3-4) Arthralgia TRAE (grade 3-4) Asthenia TRAE (grade 3-4) Blood and lymphatic system disorders TRAE (grade 3-4) Blood creatinine increased TRAE (grade 3-4) Cardiac disorders TRAE (grade 3-4) Chills TRAE (grade 3-4) Colitis TRAE (grade 3-4) Constipation TRAE (grade 3-4) Cough TRAE (grade 3-4) Decreased appetite TRAE (grade 3-4) Dermatitis acneiform TRAE (grade 3-4) Diarrhoea TRAE (grade 3-4) Dry skin TRAE (grade 3-4) Dysgeusia TRAE (grade 3-4) Dyspepsia TRAE (grade 3-4) Dysphonia TRAE (grade 3-4) Dyspnoea TRAE (grade 3-4) Eczema TRAE (grade 3-4) Endocrine disorders TRAE (grade 3-4) Epistaxis TRAE (grade 3-4) Erythema TRAE (grade 3-4) Eye disorders TRAE (grade 3-4) Fatigue TRAE (grade 3-4) Febrile neutropenia TRAE (grade 3-4) Gastritis TRAE (grade 3-4) Gastrointestinal disorders TRAE (grade 3-4) General disorders and administration site conditions TRAE (grade 3-4) Guillain-Barré syndrome TRAE (grade 3-4) Headache TRAE (grade 3-4) Hepatitis TRAE (grade 3-4) Hepatobiliary disorders TRAE (grade 3-4) Hypersensitivity TRAE (grade 3-4) Hypertension TRAE (grade 3-4) Hyperthyroidism TRAE (grade 3-4) Hypophysitis TRAE (grade 3-4) Hypothyroidism TRAE (grade 3-4) Increase AST TRAE (grade 3-4) Increased ALT TRAE (grade 3-4) Increased lipase level TRAE (grade 3-4) Infusion-related reactions TRAE (grade 3-4) Leucopenia TRAE (grade 3-4) Maculopapular rash TRAE (grade 3-4) Metabolism and nutrition disorders TRAE (grade 3-4) Mucosal inflammation TRAE (grade 3-4) Musculoskeletal and connective tissue disorders TRAE (grade 3-4) Myalgia TRAE (grade 3-4) Myocarditis TRAE (grade 3-4) Myositis TRAE (grade 3-4) Nausea TRAE (grade 3-4) Nephritis TRAE (grade 3-4) Nervous system disorders TRAE (grade 3-4) Neutropenia TRAE (grade 3-4) Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) Pancreatitis TRAE (grade 3-4) Pancytopenia TRAE (grade 3-4) Paraesthesia TRAE (grade 3-4) Peripheral neuropathy TRAE (grade 3-4) Peripheral oedema TRAE (grade 3-4) Pneumonia TRAE (grade 3-4) Pneumonitis TRAE (grade 3-4) Pruritic rash TRAE (grade 3-4) Pruritus generalised TRAE (grade 3-4) Pruritus TRAE (grade 3-4) Pyrexia TRAE (grade 3-4) Rash TRAE (grade 3-4) Renal and urinary disorders TRAE (grade 3-4) Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) Sepsis TRAE (grade 3-4) Severe skin reaction TRAE (grade 3-4) Skin and subcutaneous tissue disorders TRAE (grade 3-4) Skin exfoliation TRAE (grade 3-4) Stevens-Johnson syndrome TRAE (grade 3-4) Stomatitis TRAE (grade 3-4) Thrombocytopenia TRAE (grade 3-4) Thyroiditis TRAE (grade 3-4) Urticaria TRAE (grade 3-4) Uveitis TRAE (grade 3-4) Vascular disorders TRAE (grade 3-4) Vomiting TRAE (grade 3-4) Weight decreased TRAE (grade 3-4) Abdominal pain AE (grade 3-4) Acute kidney injury AE (grade 3-4) Anaemia AE (grade 3-4) Asthenia AE (grade 3-4) Back pain AE (grade 3-4) Blood and lymphatic system disorders AE (grade 3-4) Decreased appetite AE (grade 3-4) Diarrhoea AE (grade 3-4) Dizziness AE (grade 3-4) Dyspnoea AE (grade 3-4) Fatigue AE (grade 3-4) Febrile neutropenia AE (grade 3-4) Gastrointestinal disorders AE (grade 3-4) General disorders and administration site conditions AE (grade 3-4) Hypertension AE (grade 3-4) Hypothyroidism AE (grade 3-4) Increase AST AE (grade 3-4) Leucopenia AE (grade 3-4) Metabolism and nutrition disorders AE (grade 3-4) Mucosal inflammation AE (grade 3-4) Nausea AE (grade 3-4) Nervous system disorders AE (grade 3-4) Neutropenia AE (grade 3-4) Pneumonitis AE (grade 3-4) Rash AE (grade 3-4) Renal and urinary disorders AE (grade 3-4) Respiratory, thoracic and mediastinal disorders AE (grade 3-4) Sepsis AE (grade 3-4) Skin and subcutaneous tissue disorders AE (grade 3-4) Stomatitis AE (grade 3-4) Thrombocytopenia AE (grade 3-4) Vascular disorders AE (grade 3-4) Vomiting AE (grade 3-4) Weight decreased AE (grade 3-4)
numeric
bar chart
forest plot
medians
frequency on treatment
benefit risk analysis
Study
study type
Pathology T1 T0 Patients sample sizes ROB
Results
JAVELIN Head and Neck 100, 2021 NCT02952586 RCT laHNSCC - 1st line (L1) avelumab plus chemoradiotherapy placebo plus chemoradiotherapy previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx,or oral cavity 350 / 347 low inconclusive inconclusive 21 % increase in progression or deaths (PFS) (PE) KEYNOTE-048 (P vs C ; all population), 2019 NCT02358031 RCT mHNSCC - L1 - all population pembrolizumab cetuximab with chemotherapy (platine plus 5FU) patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 301 / 300 some concern inconclusive suggested 17 % decrease in deaths (OS) (PE) statistically significant 34 % increase in progression or deaths (PFS) (PE) statistically significant 64 % decrease in objective responses (ORR) KEYNOTE-048 (PC vs C ; all population), 2019 NCT02358031 RCT mHNSCC - L1 - all population pembrolizumab plus 5 FU plus platine cetuximab plus 5 FU plus platine patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 281 / 278 some concern conclusif demonstrated 23 % decrease in deaths (OS) (PE) inconclusive 8 % decrease in progression or deaths (PFS) (PE) suggested 28 % decrease in deaths (OS) (extension) KEYNOTE-048 (P vs C ; CPS > 20), 2019 NCT02358031 RCT mHNSCC - L1 - PDL1 positive pembrolizumab cetuximab with chemotherapy (platine plus 5FU) patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 133 / 122 some concern conclusif demonstrated 39 % decrease in deaths (OS) (PE) inconclusive 1 % decrease in progression or deaths (PFS) (PE) suggested 42 % decrease in deaths (OS) (extension) statistically significant 89 % decrease in objective responses (ORR) KEYNOTE-048 (P vs C ; CPS > 1), 2019 NCT02358031 RCT mHNSCC - L1 - PDL1 positive pembrolizumab platinium based chemotherapy (cetuximab plus 5FU and platine) patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 257 / 255 some concern conclusif demonstrated 22 % decrease in deaths (OS) (PE) inconclusive 16 % increase in progression or deaths (PFS) (PE) suggested 26 % decrease in deaths (OS) (extension) statistically significant 56 % decrease in objective responses (ORR) KEYNOTE-048 (PC vs C ; CPS > 20), 2019 NCT02358031 RCT mHNSCC - L1 - PDL1 positive pembrolizumab plus 5FU plus platine cetuximab plus 5FU plus platine patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 126 / 110 some concern conclusif demonstrated 40 % decrease in deaths (OS) (PE) suggested 27 % decrease in progression or deaths (PFS) (PE) KEYNOTE-048 (PC vs C ; CPS > 1), 2019 NCT02358031 RCT mHNSCC - L1 - PDL1 positive pembrolizumab plus 5FU plus platine cetuximab plus 5FU plus platine patients with recurrent or metastatic squamous cell carcinoma of the head and neck, untreated locally incurable recurrent or metastatic HNSCC 242 / 226 some concern conclusif demonstrated 37 % decrease in deaths (OS) (PE) inconclusive 18 % decrease in progression or deaths (PFS) (PE) EAGLE (D vs ICC), 2019 NCT02369874 RCT mHNSCC - L2 - all population durvalumab investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to curative therapy who had progression or recurrence during or after only one systemic treatment regimen containing a platinum agent 240 / 249 some concern inconclusive inconclusive 12 % decrease in deaths (OS) (PE) CheckMate 141, 2016 NCT02105636 RCT mHNSCC - L2 - all population nivolumab ICC (methotrexate, docetaxel or cetuximab) patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy 240 / 121 some concern conclusif demonstrated 30 % decrease in deaths (OS) (PE) suggested 32 % decrease in deaths (OS) (extension) KEYNOTE-040 (all population), 2018 NCT02252042 RCT mHNSCC - L2 - all population pembrolizumab chemotherapy (methotrexate, docetaxel or cetuximab) patients with recurrent or metastatic head and neck squamous cell cancer that progressed during or after platinum-containing treatment : all population 247 / 248 some concern conclusif demonstrated 20 % decrease in deaths (OS) (PE) KEYNOTE-040 (CPS >1), 2018 NCT02252042 RCT mHNSCC - L2 - PDL1 positive pembrolizumab chemotherapy (methotrexate, docetaxel or cetuximab) patients with recurrent or metastatic head and neck squamous cell cancer that progressed during or after platinum-containing treatment : only patients with CPS > 1 196 / 191 some concern conclusif demonstrated 26 % decrease in deaths (OS) (PE)