NCT01345682

LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy

Completed Phase 3 Results posted Last updated 15 February 2018

What this trial tests

Phase 3 trial testing Afatinib in Head and Neck Neoplasms in 483 participants. Completed in 6 December 2016.

Timeline

5 January 2012

Primary endpoint
15 March 2014

6 December 2016

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	483
Start date	5 January 2012
Primary completion	15 March 2014
Estimated completion	6 December 2016
Sites	101 locations across Italy, Japan, Denmark, Russia, Belgium, Sweden, Mexico, United States

Drugs / interventions tested

• Afatinib (afatinib) — full drug profile →
• Methotrexate — full drug profile →

Conditions studied

• Head and Neck Neoplasms — all drugs for Head and Neck Neoplasms →
• Carcinoma, Squamous Cell — all drugs for Carcinoma, Squamous Cell →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Head and Neck Neoplasms or Carcinoma, Squamous Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) Based on Central Independent Review Primary · From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months

PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016). The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied: * At least 20% increase in the Sum of Diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the tre

Group	Value	95% CI
Afatinib (BIBW 2992)	2.63	2.10 – 2.73
Methotrexate	1.74	1.48 – 2.40

Overall Survival (OS) Secondary · From randomization until death or study completion date (06Dec2016); Up to 60 months

Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive.

Group	Value	95% CI
Afatinib (BIBW 2992)	6.87	6.14 – 7.79
Methotrexate	6.01	5.16 – 7.75

Objective Response (OR) Secondary · Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-Progressive Dis

Group	Value	95% CI
Afatinib (BIBW 2992)	10.2	7.16 – 14.09
Methotrexate	5.6	2.58 – 10.34

Disease Control (DC) Secondary · Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (\<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-PD in NTL leads to PR * CR in TL, but not evalua

Group	Value	95% CI
Afatinib (BIBW 2992)	49.1	43.48 – 54.67
Methotrexate	38.5	30.95 – 46.49

Tumour Shrinkage Secondary · Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months

Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis. Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase. Percentage of Participants with Tumour shrinkage as per the categories (\>=20% increase, \>=0 - \<20% increase, \>0 - \<30% decrease, \>=30 - \<50% decrease, \>=50% decrease) are presented.

>=20% increase

Group	Value	95% CI
Afatinib (BIBW 2992)	16.5
Methotrexate	21.1

>=0 - <20% increase

Group	Value	95% CI
Afatinib (BIBW 2992)	24.2
Methotrexate	31.1

>0 - <30% decrease

Group	Value	95% CI
Afatinib (BIBW 2992)	23.6
Methotrexate	16.1

>=30 - <50% decrease

Group	Value	95% CI
Afatinib (BIBW 2992)	6.2
Methotrexate	4.3

>=50% decrease

Group	Value	95% CI
Afatinib (BIBW 2992)	5.0
Methotrexate	1.9

Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scor

Group	Value	95% CI
Afatinib (BIBW 2992)	11.8	± 3.16
Methotrexate	16.2	± 3.43

Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scor

Group	Value	95% CI
Afatinib (BIBW 2992)	20.0	± 3.40
Methotrexate	20.1	± 3.66

Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer \[EORTC\] quality of life questionnaires Core 30 \[QLQ-C30\], and head and neck cancer specific supplementary module EORTC QLQ-H\&N35: Pain scale from H\&N35, Swallowing scale from H\&N35 and Global health status/QoL scale from C30. Pain scale includes items 31-34 from H\&N 35; Swallowing scale includes items 35-38 from H\&N35 and Global health status/QoL scale includes items 29-30 from C30. The scores of these scales were averaged from the scor

Group	Value	95% CI
Afatinib (BIBW 2992)	28.7	± 3.54
Methotrexate	28.2	± 3.76

Status Change in Pain Scale Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.

Improved

Group	Value	95% CI
Afatinib (BIBW 2992)	26.4
Methotrexate	23.1

Stable

Group	Value	95% CI
Afatinib (BIBW 2992)	32.1
Methotrexate	31.6

Worsened

Group	Value	95% CI
Afatinib (BIBW 2992)	41.5
Methotrexate	45.3

Status Change in Swallowing Scale Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.

Improved

Group	Value	95% CI
Afatinib (BIBW 2992)	26.1
Methotrexate	23.2

Stable

Group	Value	95% CI
Afatinib (BIBW 2992)	34.2
Methotrexate	29.5

Worsened

Group	Value	95% CI
Afatinib (BIBW 2992)	39.7
Methotrexate	47.3

Status Change in Global Health Status Scale Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.

Improved

Group	Value	95% CI
Afatinib (BIBW 2992)	30.3
Methotrexate	29.1

Stable

Group	Value	95% CI
Afatinib (BIBW 2992)	26.6
Methotrexate	25.6

Worsened

Group	Value	95% CI
Afatinib (BIBW 2992)	43.1
Methotrexate	45.3

Time to Deterioration in Pain Secondary · From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Group	Value	95% CI
Afatinib (BIBW 2992)	3.02	2.83 – 3.75
Methotrexate	2.30	1.64 – 3.32

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of study medication (afatinib or methotrexate) and within 28 days after the last administration of study medication (study completion date is 06Dec2016); Up to 60 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Afatinib (BIBW 2992)

Serious: 168/320 (53%)

Deaths: —

Methotrexate

Serious: 73/160 (46%)

Deaths: —

Serious adverse events (178 terms)

Reaction	System	Afatinib (BIBW 2992)	Methotrexate
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
General physical health deterioration	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonia	Infections and infestations	—	—
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Vomiting	Gastrointestinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Asthenia	General disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Renal failure	Renal and urinary disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Mouth haemorrhage	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Malnutrition	Metabolism and nutrition disorders	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Device related infection	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Respiratory tract infection	Infections and infestations	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (42 terms — click to expand)

Reaction	System	Afatinib (BIBW 2992)	Methotrexate
Diarrhoea	Gastrointestinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Mucosal inflammation	General disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Weight decreased	Investigations	—	—
Dermatitis acneiform	Skin and subcutaneous tissue disorders	—	—
Asthenia	General disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Paronychia	Infections and infestations	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Skin fissures	Skin and subcutaneous tissue disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Acne	Skin and subcutaneous tissue disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Insomnia	Psychiatric disorders	—	—
Headache	Nervous system disorders	—	—
Conjunctivitis	Infections and infestations	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Folliculitis	Infections and infestations	—	—
Anxiety	Psychiatric disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—

Most-reported serious reactions: Malignant neoplasm progression, General physical health deterioration, Diarrhoea, Dyspnoea, Pneumonia, Tumour haemorrhage, Vomiting, Dysphagia.

Data from ClinicalTrials.gov NCT01345682 adverse events section.

Sponsor's own description

This randomised, open-label, phase III study will be performed in patients with R/M head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy. The objectives of the trial are to compare the efficacy and safety of afatinib versus methotrexate

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.
   Machiels JP, Haddad RI, Fayette J, Licitra LF, et al · · 2015 · cited 283× · PMID 25892145 · DOI 10.1016/s1470-2045(15)70124-5
2. A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.
   Seiwert TY, Fayette J, Cupissol D, Del Campo JM, et al · · 2014 · cited 131× · PMID 24928832 · DOI 10.1093/annonc/mdu216
3. HER2 as a therapeutic target in head and neck squamous cell carcinoma.
   Pollock NI, Grandis JR. · · 2015 · cited 79× · PMID 25424855 · DOI 10.1158/1078-0432.ccr-14-1432
4. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer.
   Cohen EEW, Licitra LF, Burtness B, Fayette J, et al · · 2017 · cited 57× · PMID 28961833 · DOI 10.1093/annonc/mdx344
5. Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells.
   Macha MA, Rachagani S, Qazi AK, Jahan R, et al · · 2017 · cited 41× · PMID 28423495 · DOI 10.18632/oncotarget.15468
6. Current role of EGF receptor monoclonal antibodies and tyrosine kinase inhibitors in the management of head and neck squamous cell carcinoma.
   Markovic A, Chung CH. · · 2012 · cited 40× · PMID 23098115 · DOI 10.1586/era.12.91
7. Emerging drugs for head and neck cancer.
   Wen Y, Grandis JR. · · 2015 · cited 38× · PMID 25826749 · DOI 10.1517/14728214.2015.1031653
8. New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN).
   Agulnik M. · · 2012 · cited 37× · PMID 22252310 · DOI 10.1007/s12032-012-0159-2