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D. Urban



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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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): D. Urban

      • 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.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-002 - RLIP76 expression is prognostic and predictive of chemotherapy benefit in resected NSCLC (ID 247)

      09:30 - 09:30  |  Author(s): D. Urban

      • Abstract

      Background
      Despite adjuvant chemotherapy improving overall survival of resected Stage II and III non-small cell lung cancer (NSCLC), acute and late toxicities of chemotherapy have highlighted the need to better predict which patients will benefit from treatment. RLIP76 is a ubiquitously expressed multi-functional transporter that is associated with cisplatin and vinorelbine resistance. Our aim was to analyse the prognostic and predictive value of RLIP76 expression in NSCLC.

      Methods
      We identified 367 NSCLC patients resected between 1996 and 2009. A tissue microarray was created and immunohistochemistry (IHC) performed with an anti-human RLIP76 rabbit polycloncal antibody (Millipore, Temecula, CA). The intensity (0-3) and proportion of tumour cells (0-100) with staining was scored. The product of RLIP76 intensity and proportion of tumour cells staining was calculated (range 0-300) and divided into high (>100) and no/low expression (≤100). RLIP76 expression was correlated with clinical features and patient outcome.

      Results
      IHC was available for 285 patients, 173(60.7%) of which were male. Number of patients according to stage I, II, III and IV was 150(52.6%), 83(29%), 44(15.4%) and 8(3%), respectively. RLIP76 was overexpressed in 117(41%) specimens. There was no relationship between RLIP76 expression and stage, histology, sex or age. High RLIP76 expression was associated with an improved prognosis on univariate (HR 0.62, CI 9.44-0.90, p=0.012,Figure 1) and multivariate analysis (HR 0.57, CI 0.39-0.83, p=0.003). Adjuvant chemotherapy was also associated with an improved survival on multivariate analysis (HR 0.52, CI 0.33-0.82, p=0.005). When stratifying by RLIP76 expression, the benefit of chemotherapy was limited to patients with no/low expression (HR =0.44, CI 0.24-0.8, p=0.008)(Figure 2). No benefit of chemotherapy was seen in patients with high RLIP76 expression (HR=0.75, CI 0.34-1.63, p=0.5). Figure 1 Figure 2

      Conclusion
      High RLIP76 expression is associated with an improved prognosis in resected NSCLC.Interestingly no/low RLIP76 expression may predict for benefit of adjuvant chemotherapy. Further studies are needed to confirm these results.