Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer

S Cavalieri, F Perrone, R Miceli, P A Ascierto, L D Locati, C Bergamini, R Granata, S Alfieri, C Resteghini, Donata Galbiati, A Busico, N Paielli, R Patuzzo, A Maurichi, G Gallino, R Ruggeri, L Mariani, M Palla, L Licitra, P Bossi

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Abstract

BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.

METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.

RESULTS: Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3-4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.

CONCLUSIONS: In sSCC, dacomitinib showed activity similar to what was observed with anti-epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalEuropean Journal of Cancer
Volume97
DOIs
Publication statusPublished - Jul 2018

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Squamous Cell Neoplasms
Skin Neoplasms
Epidermal Growth Factor Receptor
Safety
Radiotherapy
Drug Therapy
Mutation
Mucositis
Gene Targeting
Exanthema
Drug-Related Side Effects and Adverse Reactions
Disease-Free Survival
Fatigue
Diarrhea
Neoplasms
Therapeutics
Clinical Trials
Survival
PF 00299804
Genes

Cite this

@article{3639607c370f45a4b32d207cffe2c825,
title = "Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer",
abstract = "BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.RESULTS: Forty-two patients (33 men; median age 77 years) were treated. Most (86{\%}) received previous treatments consisting in surgery (86{\%}), RT (50{\%}) and CT (14{\%}). RR was 28{\%} (2{\%} complete response; 26{\%} partial response), disease control rate was 86{\%}. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93{\%}) experienced at least one adverse event (AE): diarrhoea, skin rash (71{\%} each), fatigue (36{\%}) and mucositis (31{\%}); AEs grade 3-4 occurred in 36{\%} of pts. In 16{\%} of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.CONCLUSIONS: In sSCC, dacomitinib showed activity similar to what was observed with anti-epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.",
author = "S Cavalieri and F Perrone and R Miceli and Ascierto, {P A} and Locati, {L D} and C Bergamini and R Granata and S Alfieri and C Resteghini and Donata Galbiati and A Busico and N Paielli and R Patuzzo and A Maurichi and G Gallino and R Ruggeri and L Mariani and M Palla and L Licitra and P Bossi",
note = "Copyright {\circledC} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
month = "7",
doi = "10.1016/j.ejca.2018.04.004",
language = "English",
volume = "97",
pages = "7--15",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer

AU - Cavalieri, S

AU - Perrone, F

AU - Miceli, R

AU - Ascierto, P A

AU - Locati, L D

AU - Bergamini, C

AU - Granata, R

AU - Alfieri, S

AU - Resteghini, C

AU - Galbiati, Donata

AU - Busico, A

AU - Paielli, N

AU - Patuzzo, R

AU - Maurichi, A

AU - Gallino, G

AU - Ruggeri, R

AU - Mariani, L

AU - Palla, M

AU - Licitra, L

AU - Bossi, P

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.RESULTS: Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3-4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.CONCLUSIONS: In sSCC, dacomitinib showed activity similar to what was observed with anti-epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.

AB - BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.RESULTS: Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3-4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.CONCLUSIONS: In sSCC, dacomitinib showed activity similar to what was observed with anti-epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.

U2 - 10.1016/j.ejca.2018.04.004

DO - 10.1016/j.ejca.2018.04.004

M3 - Article

VL - 97

SP - 7

EP - 15

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -