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• 11946

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  P2.24 - Poster Session 2 - Supportive Care (ID 157)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11987

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    P2.24-041 - A Pilot study of a Steroid Sulphatase inhibitor (BN83495) in patients with rash due to treatment with an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for non-small cell lung cancer (NSCLC) (ID 2577)

    09:30 - 09:30  |  Author(s): L. Cowan
    • Abstract

    Background
    Treatment with inhibitors of the Epidermal Growth Factor Receptor (EGFR) commonly results in rash, which causes patients significant symptoms and embarrassment, and is not always easy to manage with existing treatments. BN83495 is a first in class inhibitor of steroid sulphatase (STS), which has been used in early phase studies as treatment for steroid-dependent cancers such as breast, prostate and endometrial cancer, with one side-effect noted to be dry skin. STS converts oestrone sulphate to oestrone, a precursor of oestradiol; and dehydroepiandrosterone sulphate (DHEA-S) to dehydroepiandrosterone (DHEA), a precursor of adrenal testosterone. Blocking these pathways can be helpful in the treatment of acne, and patients with X-linked ichthyosis, who have an inherited deficiency of STS, do not get acne. Hence we hypothesized that use of BN83495 could help to treat EGFR-associated rash.

    Methods
    Eligible patients had histologically proven, locally recurrent or metastatic NSCLC and were continuing to experience rash during treatment with an EGFR-TKI (Erlotinib or Gefitinib), despite standard management. Patients were treated with BN83495 at a dose of 40 mg/day orally for a period of 12 weeks and able to continue on standard treatment for rash such as topical steroids or antibiotics. For patients with no or minimal toxicity and minimal or no rash at 12 weeks, treatment with BN83495 could continue for an additional 3 months before being discontinued. If rash worsened on discontinuation of treatment at 6 months BN83495 could be resumed. The primary objective was to describe changes in the frequency and grade of EGFR-related rash and other cutaneous side-effects of the EGFR-TKI with the combination. A pragmatic sample size of 20 patients was proposed.

    Results
    Nine patients were registered but 2 withdrew prior to commencing BN83495. All patients had grade 2 rash at study entry. Of the 7 patients who commenced study treatment, 5 had an improvement in rash by one CTC grade. Patients received BN83495 for a median of 12 weeks (range 1 – 52) with 2 patients recommencing drug after rash worsened when BN83495 was stopped after 6 months of treatment as per protocol. BN83495 was generally well tolerated with no grade 3 or 4 toxicity. However, all participants experienced grade 2 dry skin related to BN83495 which was generally manageable with moisturizers, but 2 patients stopped study drug early for this reason. 3 patients discontinued study drug when the EGFR-TKI was stopped due to disease progression, and 2 other patients elected to cease the drug at 3 and 6 months respectively because rash was mild. The study was closed early due to poor accrual as many patients were not keen to enter a study which involved treating rash by taking an additional tablet.

    Conclusion
    Treatment of EGFR-TKI related rash with the steroid sulfatase inhibitor BN83495 improved the severity of rash in the majority of patients but commonly resulted in grade 2 dry skin. Accrual to a study which involved treating rash with an additional oral medication proved challenging. Alternative approaches such as topical use of a steroid sulfatase inhibitor could be considered for further investigation.