BCC Patients Research Articles

Impact of Blood Culture Contamination on Antibiotic Use, Resource Utilization, and Clinical Outcomes: A Retrospective Cohort Study in Dutch and US Hospitals.

Blood culture contamination (BCC) has been associated with prolonged antibiotic use (AU) and increased health care utilization; however, this has not been widely reevaluated in the era of increased attention to antibiotic stewardship. We evaluated the impact of BCC on AU, resource utilization, and length of stay in Dutch and US patients. This retrospective observational study examined adults admitted to 2 hospitals in the Netherlands and 5 hospitals in the United States undergoing ≥2 blood culture (BC) sets. Exclusion criteria included neutropenia, no hospital admission, or death within 48 hours of hospitalization. The impact of BCC on clinical outcomes-overall inpatient days of antibiotic therapy, test utilization, length of stay, and mortality-was determined via a multivariable regression model. An overall 22 927 patient admissions were evaluated: 650 (4.1%) and 339 (4.8%) with BCC and 11 437 (71.8%) and 4648 (66.3%) with negative BC results from the Netherlands and the United States, respectively. Dutch and US patients with BCC had a mean ± SE 1.74 ± 0.27 (P < .001) and 1.58 ± 0.45 (P < .001) more days of antibiotic therapy than patients with negative BC results. They also had 0.6 ± 0.1 (P < .001) more BCs drawn. Dutch but not US patients with BCC had longer hospital stays (3.36 days; P < .001). There was no difference in mortality between groups in either cohort. AU remained higher in US but not Dutch patients with BCC in a subanalysis limited to BC obtained within the first 24 hours of admission. BCC remains associated with higher inpatient AU and health care utilization as compared with patients with negative BC results, although the impact on these outcomes differs by country.

Transforming growth factor-b1 and soluble co-inhibitory immune checkpoints as putative drivers of immune suppression in advanced basal cell carcinoma.

9567 Background: BCC rarely metastasizes and the mortality rate is low; however, the disease is associated with substantial morbidity. Transforming growth factor-b1 (TGF-b1) is a key player in cell proliferation, differentiation, apoptosis, and immune regulation. TGF-b1 is associated with immunosuppression and resistance to immunotherapeutic drugs. Immune checkpoint proteins (ICMs) maintain self-tolerance and modulate the immune responses of effector cells. The current study compared the levels and possible associations between systemic soluble ICMs (sICMs) and a group of humoral modulators of immune suppressor cells in a cohort of patients with advanced basal cell carcinoma (BCC, n = 40) and a group of healthy control subjects (n = 20). Methods: We measured sICMs and immunosuppressive humoral modulators by using multiplex bead array or ELISA procedures, with plasma as the matrix. The sICMs comprised seven co-inhibitory (CTLA-4, BTLA, LAG-3, PD-1, PDL-1, PDL-2, and TIM-3) and eight co-stimulatory (CD27, CD28, CD40, CD80, CD86, GITR, GITRL, and ICOS) proteins, as well as the two dual-active sICPs, HVEM and TLR2. The seven humoral modulators of immunosuppressor cells included arginase 1, fibroblast activation protein (FAP), RANTES (Regulated upon Activation Normal T Cell Expressed and Presumably Secreted) also known as CCL5, interleukin-10 (IL-10), TGF-b1, and the M2-type macrophage biomarkers, soluble CD163 (sCD163) and sCD206. Ethics approval was granted by The Research Ethics Committee, Faculty of Health Sciences, University of Pretoria (Ethics Committee Approval Numbers 356/2020. Results: The plasma levels of six co-inhibitory sICPs, sCTLA-4, sLAG-3, sPD-1, sPD-L1, and sTIM-3 and sPD-L2 were significantly elevated in the cohort of BCC patients ( p&lt; 0.001- p&lt; 0.00001), while that of sBTLA was significantly decreased ( p&lt; 0.006). Of the co-stimulatory sICPs, sCD27 was significantly increased ( p &lt;0.0002) in the cohort of BCC patients, with the levels of the others essentially comparable with those of the control patients; of the dual active sICPs, sHVEM, sTLR2 was significantly elevated ( p&lt; 0.00001) and TLR2 comparable with the control group. Although the plasma levels of the seven modulators of immune suppressor function were not significantly different between the BCC and control groups, correlation heat maps revealed selective, strong associations of TGF-b1 with seven co-stimulatory (z = 0.618468-0.768131) and 4 co-inhibitory (z = 0.674040-0.808365) sICPs, as well as with sTLR2 (z = 0.696431). Conclusions: Notwithstanding the association of BCC with selective elevations in the levels of a large group of co-inhibitory sICPs, our novel findings also imply the probable involvement of TGF-b1 in driving immunosuppression in this malignancy, possibly via activation of regulatory T cells.

CO175 Systematic Literature Review of Outcomes in Patients With Advanced Basal Cell Carcinoma (ABCC) Who Progressed on or Are Intolerant to Hedgehog Inhibitors (HHI)

Cemiplimab is the first treatment approved in patients with aBCC who have progressed on or are intolerant to an HHI based on Study 1620 (NCT03132636), an open-label, multicentre, single arm, non-randomised trial. Prior to cemiplimab availability, there was no standard of care after HHI for advanced BCC patients. The objectives of the current study were to identify and characterise clinical trials and observational studies evaluating the response rates, progression-free survival, or overall survival (OS) of patients with aBCC following HHI receiving systemic therapy or best supportive care (BSC).

32283 A phase I study of CX-4945 administered orally twice daily to patients with advanced basal cell carcinoma

Background: Smoothened inhibitors (SMOi) targeting the hedgehog (Hh) pathway have been approved for the treatment of patients with locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). Unfortunately, resistance against SMOi can develop. Targeting the signaling cascade downstream of SMO could obviate this issue. Casein kinase 2 (CK2) affects the terminal component of the Hh signaling pathway by promoting Gli2 stability and Gli2’s interaction with target genes. Given the interplay between CK2 and Gli-2, CX-4945 may provide benefit for BCC patients with resistance or intolerance to SMOi. Methods: A phase I trial to explore various treatment durations of CX-4945 was designed for patients with laBCC or mBCC; with endpoints including safety and objective response rate. Major eligibility criteria include progression after SMOi. The first phase of the trial uses a 3+3 design to test the tolerance of a CX-4945 dose of 1000 mg BID for a duration of 28 days continuously. Upon determining the RP2D, a dose-expansion phase will further evaluate CX-4945 in 10 patients with laBCC. Results: As of September 1, 2021, 15 patients with BCC were enrolled. The most common grade 3 treatment-related adverse event was GI related, diarrhea (13%). No grade 4 events were reported. Among the 13 patients who were evaluable for response at end of cycle 2, 2 patients (15%) demonstrated a partial response. The expansion phase is currently enrolling patients. Complete safety and efficacy data will be presented after completion of phase 1.

Vismodegib in Locally Advanced Basal Cell Carcinoma in Slovenia

Background: Vismodegib is a first-in-class inhibitor of the hedgehog pathway for treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC. Objectives: The purpose of this study is to report outcomes of patients with laBCC, with basal cell carcinoma nevus syndrome (Gorlin Goltz syndrome [G-G Syn]) treated with vismodegib in routine clinical practice in Slovenia in 8.3-year period. Methods: In this retrospective cohort study, we analyzed baseline characteristics, outcomes, and treatment-related adverse events from locally advanced BCC. The patients were divided into two cohorts: 39 laBCC or multiple BCC patients and 7 patients with G-G Syn who were treated with vismodegib from November 2012 till January 2021. Results: During 100-month period, 46 patients were diagnosed with laBCC (26), multiple BCC (13), and G-G Syn (7), all inappropriate for surgery or radiotherapy. Baseline characteristics: median age was 72.8 years in laBCC + multiple BCC cohort and 47.4 years in G-G Syn cohort. The objective response rate was 80% in laBCC + multiple BCC and 86% in G-G Syn cohort. Disease control rate (DCR) was 95% in laBCC + multiple BCC and 100% in G-G Syn cohort. Median duration of treatment was 9.9 months (range: 1.5–43.1) in laBCC and multiple BCC cohort and 19.5 months (range: 3.6–94.1) in G-G Syn cohort. Majority of treatment-emergent adverse events (TEAEs) in laBCC or multiple BCC cohort were grade 1 or 2 (96%), only 4% of AEs were grade 3. Majority of TEAEs in G-G Syn cohort were also grade 1 or 2 (87%), 13% of AEs were grade 3. No grade 4 or 5 vismodegib-related AEs were reported. Conclusion: Vismodegib has shown meaningful efficacy with DCR from 95% to 100% in patients with laBCC, multiple BCC, and G-G Syn in Slovenia. TEAEs were successfully alleviated with multidisciplinary approach and early supportive care.

A facelift procedure for resection of a branchial cleft cysts

ObjectivesBranchial cleft cysts (BCCs) are common in daily practice, however, BCC patients suffer aesthetic problems due to postoperative scars on visible parts after surgery. To analyze the feasibility, surgical outcomes and possible risks and complications encountered during a facelift procedure for patients with BCC. MethodsThis retrospective analysis examined patients who had undergone surgery for branchial cleft cyst using a facelift procedure (n = 16) or conventional transcervical resection (n = 20) at our institutes between April 2015 and August 2021. ResultsThere was no significant difference between the groups that underwent the facelift procedure or conventional transcervical resection as to the average size of the cysts, operating time, bleeding, drain out, or recurrence. None of the patients needed to switch from the facelift procedure to conventional transcervical resection. In all the patients in the facelift procedure group, postoperative scars were fully concealed by the auricle and hair. However, four patients in the facelift procedure group experienced a transient auricular complication after surgery. ConclusionThe facelift procedure provides adequate visualization, workspace and excellent cosmetic results in suitably selected cases with BCC.

215 BCC Management in the UK and Overseas. an Audit of a Single Surgeon's Experience

Abstract Aim To compare the management of BCC in a single surgeon’s practice and audit of practice against the British Association of Dermatologist (BAD) recommendations. To see any differences in terms of management in two different setups and patient population. Method Retrospective data collection and statistical analysis comparing the practice in Pakistan between 2011–2014 and recent practice in the NHS at Bradford Teaching Hospitals Foundation Trust from August 2020 to March 2021 Results 53 BCC patients were identified in the UK with a mean age of 71 compared to 64 overseas patients with a mean age of 62. The most common anatomical region for both groups was the face. The histology reports showed a discrepancy to the number of details enlisted. In the overseas group the BCC subtype was not mentioned in 72% of the reports as well as no reporting of clark's level or TNM staging. The mean reporting time was 5 days in the overseas group compared to 8 days in the UK group. Conclusions The British Association of Dermatologists has set standards for management of Basal Cell Carcinoma including surgical margins and histological reporting. Areas of improvement have been identified according to those guidelines.

The initial rate of tumour response to vismodegib treatment, can predict a complete response outcome for periocular LA-BCC.

To establish a model to predict treatment outcome of periocular locally advanced basal cell carcinoma (POLA BCC) based on initial response to treatment with vismodegib (ErivedgeTM), a sonic hedgehog inhibitor. Subgroup analysis of data from the STEVIE study database. Analysis of medical history, treatment protocol, and treatment outcome of POLA BCC tumours in a STEVIE study population of 244 POLA BCC patients treated with ≥1 dose of vismodegib. A predictive model for complete response (CR) was established based on the initial treatment response. A cutoff value of 20% reduction in tumour size at 3 months of treatment identified the patients with a high probability (82.76%) to achieve CR. A second cutoff value of 67.7% reduction in tumour size at 6 months of treatment improved the prediction to a 95.42% probability of a CR outcome. A treatment model was constructed based on the prediction of a CR outcome and the initial response to vismodegib treatment at 3 and 6 months. The study result provide significant new insights can facilitate decision-making on treatment management according to tumour response in patients with POLA BCC.

Role of Bcl-2, p53, and Ki-67 expression in basal cell carcinoma and their association with aggressive and non-aggressive histological phenotypes.

IntroductionThere is increasing evidence that immunohistochemical expression of p53, Ki-67, and Bcl-2 is associated with aggressive (aBCC) and less aggressive (nBCC) histological subtypes and may have a prognostic role.AimTo investigate the clinicopathological features and immunohistochemical expressions of p53, Ki-67, and Bcl-2 in cutaneous basal cell carcinoma focusing on histological subtypes. Their roles and possible interactions in the development and progression of BCC are discussed.Material and methodsA total of 50 BCC samples from 50 patients from Western Mexico between June 2018 and June 2019 were included. Paraffin-embedded samples were immunostained with p53, Ki-67, and Bcl-2 antibodies. Semi-quantitative analysis was performed to determine the intensity and positivity of immunostained cells. Parametrical and non-parametrical tests were performed according to the sample’s distribution.ResultsSamples included 21 nBCC and 29 aBCC. The statistical analysis showed statistical association when grouped as non-aggressive and aggressive subtypes for p53 (p = 0.04) and Bcl-2 (p < 0.01). An inverse negative correlation was found between age and Bcl-2 expression. No statistical association was found between Ki-67 immunoreactivity and any of the other variables.ConclusionsWe found that a high expression of Bcl-2 and a low expression of p53 was associated with more indolent histopathological features of BCC and therefore better outcomes. These findings suggest that examination of p53 and Bcl-2 expression in BCC patients may provide valuable prognostic information. These biomarkers may play a role in the development and progression of some cases of BCC.

Clinical and histopathological characteristics of primary and recurrent basal cell carcinoma: a retrospective study of the patients from a tertiary clinical centre in the northern Poland.

IntroductionBasal cell carcinoma (BCC) is the most common malignant neoplasm of the skin. Management of patients with recurrent BCC remains a current clinical issue. Data concerning BCC recurrence rates as well as characteristics of this group of patients in the Polish population are scarce.AimIdentification and analysis of clinical, epidemiological and histopathological factors influencing BCC recurrence.Material and methodsHistopathological diagnoses of BCC patients treated by surgical methods at the Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, between 2013 and 2018, were retrospectively analysed. The analysis included 1097 tumours diagnosed in 802 patients, of which 1061 were primary BCC (pBCC) and 36 – recurring BCC (rBCC).ResultsIn the analysed cohort, rBCCs constituted 3.3% of cases. 49.8% of pBCCs occurred in women; while in the rBCC group – 47.2%. The most common histopathological type was infiltrative BCC, however, it was significantly more prevalent in rBCCs (36.9% and 52.8%, respectively). The average maximum size of pBCC was 12.3 ±8.8 mm, while of rBCC 18.4 ±15.1 mm (p = 0.036). The most common location of both pBCC and rBCC was the nose (tumours in this localization constituted 23.2% and 25.0%, respectively).ConclusionsIn the analysed cohort a relatively low percentage of rBCC was found. Among analysed risk factors, the most important ones were the infiltrative histopathological type of BCC and the non-radical treatment of the primary tumour.

Prognostic Factor of H-Zone Area in Basal Cell Carcinoma

The study data were taken from secondary data obtained from medical records of BCC patients in Dr. Moewardi Hospital. The data were categorized based on gender, age, occupation, predilection/ location of tumor based on Baxter criteria, which divided the area into H-zone dan non-H-zone. H-zone was described to cover temporal, auricular, orbital, nasal, upper mandibular. Whereas the tumor size was divided into two, less than 2 cm and more than 2 cm. H-zone is a predilection with a high risk toward tumor biological characteristics, such as recurrence risk, aggressivity risk, and tumor infiltrative. The study obtained an ethics clearance from Health Research Ethics Committee of Dr. Moewardi Hospital with number 762/VIII/HREC/2021. The analysis was conducted to test whether there was a correlation or effect between two variables or more. In the study, the researcher also conducted statistics test to measure the correlation intensity of two variables or more by using Chi-square (X2), statistics test was conducted by using SPSS 22 for Windows. 99 patients were obtained from the medical records however only 70 patients who met the study requirements, who were subsequently categorized based on gender, age, occupation, BCC location and size, disease duration. 29 patients were excluded due to incomplete medical records (BCC location, BCC size, and treatment history were not found) non-primary BCC, data duplication, patients with more than one medical records, the result of histopathological test did not indicate seborrheic keratosis and Squamosa Cell Carcinoma. Based on the study there were more female patients compared to male patients. it discovered 45 female patients and 25 male patients (64,3% compared to 35,7%), with the age range was from 22-90 years, the BCC tumor was endured for more than 2 years, based on the education most of the patients had primary education background (elementary school and junior high school), the majority occupation of the patients was farmer (30%), followed by housewife (28,57%).

Dermoscopy-guided Mohs micrographic surgery in post-laser basal cell carcinomas: is dermoscopy helpful for demarcation of the surgical margin?

Background Mohs micrographic surgery (MMS) in cases where the tumor margin is poorly defined to the naked eye can lead to the need to take an increased number of Mohs stages. Objective To evaluate the usefulness of dermoscopy in determining MMS surgical margins of BCCs with a history of ablative laser treatment. Methods Patients were randomly allocated to naked eye (n = 69) or dermoscopy (n = 64) groups by the surgical margin detection method. Surgical outcomes of 133 post-laser BCC patients treated with MMS were analyzed. Results The lateral margin involvement rate at the first MMS stage was significantly lower in the dermoscopy group than in the naked eye group (4.7% vs. 29.0%; p < .001). However, the deep margin involvement rate at the first and mean MMS stages were not significantly different between the groups. The ablative laser treatment duration correlated to the number of MMS stages (p = .026). Conclusion The results demonstrated that lateral margin was mostly controlled within the first MMS stage with dermoscopy. Dermatosurgeons could focus on the deep margin after the first MMS stage; thus, the performance of MMS could be improved with dermoscopic assistance in post-laser BCC patients.

A phase I study of CX-4945 administered orally twice daily to patients with advanced basal cell carcinoma.

TPS10080 Background: Smoothened inhibitors (SMOi) targeting the Hedgehog (Hh) pathway have been approved for the treatment of patients with locally advanced Basal Cell Carcinoma (laBCC) or metastatic BCC (mBCC). Unfortunately, resistance against SMO inhibitors (SMOi) can develop. Targeting the signaling cascade downstream of SMO, in this case via a novel small molecule inhibitor, could obviate this issue. Casein Kinase 2 (CK2) affects the terminal component of the Hh signaling pathway by promoting Gli2 stability and Gli2’s interaction with target genes. Given the interplay between CK2 and GLI-2 and the importance of Hh signaling activation, CX-4945, a potent CK2 inhibitor, may provide benefits for the BCC patients with resistance or intolerance to SMOi. Methods: A phase I trial (NCT03897036) to explore various treatment durations of CX-4945 was designed for patients with laBCC or mBCC; with endpoints include safety (CTCAE v5) and objective response rate by RECIST 1.0 for mBCC and composite response for laBCC. Major eligibility criteria include progression or intolerability to SMO inhibitors; laBCC patients must not be surgical candidates and must have received prior radiation unless contraindicated, and basosquamous histology is excluded. The first phase of the trial uses a 3+3 design to test the tolerance of a CX-4945 dose of 1000 mg bid for a duration of 28 days continuously. If 2 out of 3, or 2 out of 6 patients experience a DLT, the regimen of 1000 mg bid for 21 days followed by 7 days off (already tested in prior CX-4945 Phase I trials in other tumor types) will be selected as the recommend phase 2 dose (RP2D). Upon determining the RP2D, a dose-expansion phase will further evaluateCX-4945 in two cohorts (laBCC &amp; mBCC), with 10 patients enrolled in each. Currently, we are enrolling patients and collecting sufficient data for the determination of RP2D in this patient population; thus, further assessments are required to determine the safety, tolerability, and efficacy of CX-4945 in advanced BCC. Clinical trial information: NCT03897036.

MIF functional polymorphisms (−794 CATT5–8 and −173 G&amp;gt;C) in Basal Cell Carcinoma in western Mexican population

Abstract Basal cell carcinoma (BCC) is the dermatological neoplasm more prevalent worldwide, in recent years there has been an increase in the number of cases becoming a health problem. Despite its high incidence, there is little information about genetic factors that lead to the carcinogenesis of this neoplasms. In the last years, macrophage migration inhibitory factor (MIF) has received particular attention, its expression has been linked to the development of different types of cancer. Therefore, the aim of this study was to investigate the genetic association of −794 CATT5–8 and −173 G&amp;gt;C MIF polymorphisms with BCC. A total of 150 BCC patients and 150 individuals with similar age than cases as a control group were recruited. Total genomic DNA was extracted from peripheral blood leukocytes by the salting out method. The −794 CATT5–8 MIF polymorphism was analyzed by conventional PCR and polyacrylamide gel electrophoresis, the −173 G&amp;gt;C MIF polymorphism was genotyped by PCR-RFLP as was done in previous studies by our research group. It was found that BCC incidence is higher in women than men additionally the localization of this neoplasia are more prevalent in head and neck. Also, it was found that the 5/5 genotype of the −794 CATT5–8 MIF polymorphisms of confers a risk to BCC development (OR=4.55, p=0.04). Respect to the −173 G&amp;gt;C MIF polymorphism we did not find a statistical difference. In conclusion, our findings suggest that the 5/5 genotyope of −794 CATT5–8 MIF polymorphism is associated with the development of BCC in patients from western Mexico. Further studies are needed due to the relation of the functions of MIF and de development of cancer.

Investigation of Interleukin-27 in the Sera of Nonmelanoma Skin Cancer Patients.

IL-27 has been shown to have both tumor promoting and suppressing functions. IL-27, with its diverse influences on immune responses, has not been studied extensively in nonmelanoma skin cancers (NMSC), including Squamous and Basal Cell Carcinomas (SCC and BCC), and its roles in tumor initiation, progression, and its probable use in NMSC treatment have yet to be unveiled. A cross-sectional analytical study was designed to investigate the serum levels of IL-27 in NMSC patients in comparison to normal individuals. Levels of IL-27 in the sera of 60 NMSC patients along with 28 healthy controls were measured by means of quantitative enzyme-linked immunosorbent assay (ELISA). In this study we observed that IL-27 serum levels were significantly higher in NMSC patients in comparison to healthy individuals (0.0134 versus 0.0008 ng/ml; P<0.001). Furthermore, when subcategorized based on pathological diagnosis, both BCC and SCC patients had higher levels of IL-27 in their sera compared to controls (P=0.002 and P=0.033; respectively). However, these levels were not different among SCC and BCC patients. According to our results, it seems that IL-27 is involved in antitumor immune responses in NMSCs. On the other hand, these observations might be indicative of this cytokine involvement in NMSC tumorigenesis and progression. Therefore, administration of this cytokine for therapeutic purposes in patients with such conditions should be erred on the side of caution.

IMPROVING THE MODEL FOR THE UK MS DISEASE MODIFYING TREATMENT RISK SHARING SCHEME ANALYSIS: A NEW NATURAL HISTORY DATASET

BackgroundAlthough in 2002 the National Institute for Clinical Excellence, in 2002, concluded that the disease modifying treatments (DMTs) for MS–interferon–b and glatiramer acetate–were not cost effective over the short–term, it...

Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma

The pathogenesis of BCC is associated with sonic hedgehog (SHH) signaling. Vismodegib, a smoothened inhibitor that targets this pathway, is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. We studied gene expression profiling of BCC tumour tissues coupled with laser capture microdissection to identify tumour specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. We found a >250 fold increase (FDR<10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger expression of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01). Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promote keratinocyte proliferation. Hence, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients.

1111PD - Expanded Access Study of Advanced Bcc Patients Treated with the Hedgehog-Pathway Inhibitor Vismodegib

ABSTRACT Background Patients (pts) with advanced basal cell carcinoma (aBCC; disease that is locally advanced [laBCC] or metastatic [mBCC]) have limited therapeutic alternatives. The Hedgehog signaling pathway is a key driver in the pathogenesis of BCC. In a pivotal Phase II study, vismodegib (Erivedge™)—a first-in-class small-molecule inhibitor of Hedgehog pathway signaling—demonstrated significant clinical activity in aBCC with an acceptable safety profile. This US-only expanded access study initiated prior to FDA approval, provided vismodegib for aBCC pts and further characterized its safety profile and clinical activity. Methods Pts with histologically confirmed mBCC or laBCC inappropriate for, or recurring after surgery or radiotherapy, received daily oral vismodegib 150 mg until disease progression or intolerable toxicity. Interim data for the first 96 pts, enrolled Jul 2010–Nov 2011, are summarized; final results will be presented at the meeting. Results Of 96 pts (52 laBCC, 44 mBCC), 74% were male; median age was 63 (28–100) years. Median disease duration from diagnosis was 3.6 (0.02–53.2) years. Prior treatments included surgery (92%) and radiotherapy (51%). Pts received vismodegib for a median of 4.3 (0.6–16.1) months (median follow-up [f-u] 4.7 [0.6–16.1] months). Treatment-emergent adverse events (AEs) of any grade in ≥15% pts were: muscle spasms (60.4%), dysgeusia (55.2%), alopecia (45.8%), diarrhea (17.7%), nausea (17.7%), and fatigue (17.7%), with median times to first event of 30, 36, 84, 27, 25, and 22 days, respectively. No serious AEs related to vismodegib were reported. Discontinuations (n = 26) were due to disease progression (n = 14), AEs (n = 3), death (n = 1), lost to f-u (n = 1), physician (n = 1) or subject decision (n = 5), or other (n = 1). Of 69 evaluable patients with RECIST-measurable disease, the investigator-assessed response rate was 20/40 (50%; 95% CI 34–66%) for laBCC and 10/29 (34%; 95% CI 18–54%) for mBCC. 16 pts (40%) with laBCC and 14 (48%) with mBCC had stable disease. Conclusions Incidence and severity of AEs and clinical activity reported in this analysis are similar to those reported in the pivotal study in pts with aBCC. Vismodegib is an effective treatment option for aBCC pts. Disclosure G.J. Weiss: Speaker's bureau: Genentech, Pfizer Funding to my institution: Genentech, Novartis, Eli Lilly, Infinity. A. Oro: Trial funding: Genentech, Novartis, Infinity. A.L.S. Chang: Studies sponsored: Genentech, Novartis, Infinity, NuSkin, Galderma. J.A. Solomon: Advisory Committee/Group: Genentech P.M. LoRusso: Research funding: Genentech Advisory Board: Genentech Speakers' Bureau: Genentech. O. Hamid: Consulting fee: Genentech Speaker bureau: BMS, Lilly, Genentech, Dendreon Research fee: GSK, Roche, merck, ArQule, Morphotek, EISAI, Lilly, BMS, Millenium. D.M. Chen: Employee: Genentech Shareholder: Genentech. E. McKenna: Employee: Genentech Shareholder: Genentech. S. Feng: Employee: Genentech Shareholder: Genentech. All other authors have declared no conflicts of interest.

Demographic and treatment characteristics for advanced basal cell carcinoma (aBCC) in an oncology outpatient setting.

e19001 Background: aBCC is defined as (1) locally advanced BCC (inoperable or surgery contraindicated) with disease progression after radiation (unless radiation contraindicated), or (2) metastatic BCC. Information on aBCC patient demographics, or clinical and treatment characteristics is limited. The purpose of this descriptive study is to characterize aBCC patients receiving care within the US Oncology (USO) network. Methods: Patients with a diagnosis of aBCC between July 1, 2006 to June 30, 2010 were included. From an initial pool of 278 BCC patients, AJCC staging 6th ed. (Stage III, IV) and metastatic status were used to identify aBCC patients. Detailed Electronic Medical Records (EMR) and physical chart reviews were conducted on identified patients to collect information on patient demographics, clinical characteristics, and current and historical treatment characteristics. Analyses were primarily descriptive. Results: 41 patients were treated at USO clinics for aBCC. Mean age was 72 years, males comprised 68%, and mean Charlson Comorbidity Score was 0.97. 11 patients developed metastases. Sites of advanced disease were in the head/neck area (54%), extremities (10%), trunk (5%) and other (32%). Before progression to aBCC, patients received BCC-related surgeries (12 or 29%), radiation (9 or 22%) and chemotherapy (1 or 2%) while post aBCC diagnosis, patients received surgeries (24 or 59%), radiation (28 or 68%) and chemotherapy (13 or 32%), where each patient could have more than one procedure. Before progression to aBCC, there were 2 Moh’s surgeries and 2 excisions while post aBCC diagnosis, there were 6 Moh’s surgeries and 15 excisions. Among 20 chemotherapy regimens post diagnosis to aBCC, 15 were platinum based. These patients saw several types of physicians, namely radiation oncologists (34%), medical oncologists (29%), dermatologists (21%), surgical specialists (12%), and primary care physicians (4%). Conclusions: aBCC is an uncommon but serious condition, for which there appears to be no commonly accepted approach to therapy. Even in a national oncology community group, there is no consistent pattern of care for aBCC patients, suggesting that more research and options are needed.

Sun Exposure May Offer Mortality Benefit in BCC Patients

Sun Exposure May Offer Mortality Benefit in BCC Patients