The Fourth Annual World Cutaneous Malignancies Congress

The Fourth Annual World Cutaneous Malignancies Congress (WCMC) took place in Seattle, WA, on July 24-25, 2015. The WCMC is a 2-day congress dedicated to informing, educating, and fostering the exchange of clinically relevant information in the field of cutaneous malignancies on topics in melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and cutaneous T-cell lymphoma. The following abstracts were presented at the meeting.

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CATEGORY VI: Targeted therapies

Composite Assessment of Treatment Response in Patients with Locally Advanced Basal Cell Carcinoma: Sonidegib Efficacy Using 2 Sets of Response Criteria

Reinhard Dummer,¹ Vernon K. Sondak,² James Grichnik,³ Lawrence Schwartz,⁴ Sven Gogov,⁵ Tingting Yi,⁶ Manisha Mone,⁶ Aldo Trylesinki,⁵ Dalia Sellami,⁶ Michael Migden^7
1University Hospital Zurich, Zurich, Switzerland; ²H. Lee Moffitt Cancer Center, Tampa, FL, USA; ³University of Miami, Miller School of Medicine, Miami, FL, USA; ⁴Columbia University Medical Center, New York, NY, USA; ⁵Novartis Pharma AG, Basel, Switzerland; ⁶Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; ⁷The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Background: In the pivotal BOLT phase 2 study (NCT01327053), durable responses were observed in pts with advanced BCC treated with sonidegib, a Hedgehog pathway inhibitor (HPI). Treatment responses were assessed using a novel composite evaluation, which was more stringent than that used in prior studies of HPIs in BCC. Objectives: In this analysis, treatment responses in BOLT were evaluated using 2 sets of criteria: BCC-mRECIST (A; used in BOLT) and BCC-mRECIST-like (B; similar to criteria used in other HPI studies with less stringent requirements for complete response [CR]). Methods: Assessments by MRI per RECIST v1.1, photography per WHO guidelines, and histology in multiple biopsies were used to determine a composite overall response (COR) in pts with locally advanced basal cell carcinoma (laBCC) treated with sonidegib 200 mg once daily (QD) using criteria A and B. The main distinction between A and B was the level of stringency required to achieve a COR of CR. Criteria B allowed a COR of CR when there was any response (CR or PR) by MRI or photography, as long as the histology result was negative; in contrast, in the same cases, a COR per criteria A required CR (or CR equivalent) for all image modalities used and negative histology. Objective response rate (ORR), best overall response (BOR), and disease control rate (DCR; CR + PR + SD) were assessed by central review using both criteria (12-mo data; cutoff: Dec 31, 2013; median follow-up: 20 mo). Results: The ORR and DCR were similar with both criteria, but the CR rate was higher with criteria B than with A (20% vs 5%). Efficacy of sonidegib 200 mg QD in pts with laBCC: criteria A vs B (all %; n=66); ORR: 58 vs 62 (95% CI, 45-70 vs 49-74); BOR: CR: 5 vs 20; PR: 53 vs 42; SD: 33 vs 29; Progressive disease: 2 vs 2; Unknown: 8 vs 8; DCR: 91 vs 91. Conclusion: These data demonstrate a high response to sonidegib and the stringency of the BCC-mRECIST criteria used in BOLT. The higher CR rate with the BCC-mRECIST-like criteria observed in this analysis was due to the less stringent requirement for a COR of CR (ie, negative histology can overrule MRI/photography data that indicate residual disease). Despite the inherent challenges of assessing tumor response in laBCC, both evaluation criteria support the clinical benefit of sonidegib in this difficult-to-treat pt population.

Overall Survival of Metastatic Melanoma (mM) Patients Treated with High Dose IL-2 (HD IL-2) Followed by Immune Checkpoint Blockage of the CTLA-4 or the Programmed Death (PD-1/PD-L1) Pathways: Analysis of Data on the Current Use of HD IL-2

Michael K. K. Wong¹; Michael A. Morse²; David F. McDermott³; Joseph Clark⁴; Howard Kaufman⁵; Gregory A. Daniels⁶; Hong Hua⁷; Sandra Aung^7
1Department of Medicine, University of Southern California, Los Angeles, CA, USA; ²Duke University Medical Center, Durham, NC, USA; ³Beth Israel Deaconess Medical Center, Boston, MA, USA; ⁴Loyola University Medical Center, Maywood, IL, USA; ⁵Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; ⁶University of California San Diego, Moores Cancer Center, La Jolla, CA, USA; ⁷Prometheus Laboratories Inc, San Diego, CA, USA

Background: The PROCLAIM^SM registry (www.proclaimregistry.com), created in 2011, is the largest collection of IL-2 treated patients in the US and provides real-time insights into sequencing or combining IL-2 with new and old therapies and how this may affect patient outcomes. Previously, we reported a median overall survival (mOS) of 20 months with a median follow-up of 37 months in mM patients treated with HD IL-2 between 2007 and 2012 from a retrospective cohort. These findings led to the hypothesis that improved mOS may have been a result of subsequent salvage therapies, including checkpoint inhibitors. Objectives: To report on the analysis of survival data from 26 sites. Methods: Patients must have received at least 1 dose of HD IL-2 for this analysis. Those who received checkpoint therapy prior to HD IL-2 were excluded. Statistics and survival analysis on prospectively entered patients were performed on data sets as of March 16, 2015. Results: The mOS for the 236 patients was 18.4 months, with a median follow-up of 21.7 months. Patients were stratified into 3 groups; HD IL-2 only (n = 123), HD IL-2 followed by ipilimumab (post ipi, n = 78), and HD IL-2 followed by PD-1/PD-L1 inhibitors (post ?PD-1, n = 35). Patients in the HD IL-2 only, post ipi, and post ?PD-1 groups achieved a mOS of 14, 15.7, and 28.7 months, respectively. The estimated 12-month survival rates were 56%, 64%, and 97%, respectively. There were 10/78 (13%) and 3/35 (8.6%) posttherapy treatment-related incidences of autoimmune events in the post ipi and post ?PD-1 groups, respectively. No treatment-related deaths were reported. Conclusions: This is the first report of clinical data relating to HD IL-2 use followed by checkpoint blockage of the PD-1/PD-L1 pathway. Treatment with anti–PD-1/PD-L1 after initial therapy with HD IL-2 had significantly prolonged survival compared with patients treated with ipilimumab. Moreover, improved survival was not observed in patients treated with follow-on ipilimumab compared with patients treated only with HD IL-2. Anti–PD-1/PD-L1 therapy after HD IL-2 appears to be safe and is therapeutically active. These data support the concept of investigating IL-2 therapy in combination or sequence with newly developed immune checkpoint inhibitors.