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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
- Source :
- European journal of cancer (Oxford, England : 1990). 97
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Oncology
Neuroblastoma RAS viral oncogene homolog
Male
Cancer Research
medicine.medical_specialty
Skin Neoplasms
medicine.medical_treatment
Dacomitinib
Skin cancer
Skin squamous cell carcinoma
Aged
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Squamous Cell
Female
Follow-Up Studies
Humans
Lymphatic Metastasis
Middle Aged
Prognosis
Quinazolinones
Survival Rate
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Mucositis
80 and over
Adverse effect
Chemotherapy
Tumor
business.industry
Carcinoma
medicine.disease
Rash
Clinical trial
Radiation therapy
030104 developmental biology
chemistry
Squamous Cell
030220 oncology & carcinogenesis
medicine.symptom
business
Biomarkers
Subjects
Details
- ISSN :
- 18790852
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Accession number :
- edsair.doi.dedup.....3dcf460e4d3642887155a71c7493e2dc