Displaying One Session

Room 324 Mixed Proffered paper and Mini oral session
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Location
Room 324
Chairs
  • Reinhard Dummer
Mixed session - Melanoma Mixed Proffered paper and Mini oral session

341O - Clinical and FDG-PET markers of immune checkpoint inhibitor (ICI) response in patients with metastatic Merkel cell carcinoma (mMCC)

Presentation Number
341O
Lecture Time
02:30 PM - 02:42 PM
Speakers
  • Alison M. Weppler
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Alison M. Weppler
  • Prachi Bhave
  • Paolo De Ieso
  • Margaret Chua
  • Jeanette Raleigh
  • Athena Hatzimihalis
  • Anthony Gill
  • Shiva Balachander
  • Jason Callahan
  • Andrew Pattison
  • Alex Caneborg
  • George Au Yeung
  • Grant McArthur
  • Rodney J. Hicks
  • Richard Tothill
  • Shahneen K. Sandhu

Abstract

Background

mMCC is a rare, highly aggressive neuroendocrine cancer of the skin with a poor prognosis. ICIs have favourable efficacy and safety in clinical trials. We outline single centre experience utilising ICIs in mMCC.

Methods

Medical records of patients (pts) with mMCC treated with ICIs from Aug 2015 to Dec 2018 at Peter MacCallum Cancer Centre in Australia were retrospectively analysed. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples were performed. Baseline tumor volumes and responses were assessed with FDG-PET scans using the Hicks criteria.

Results

23 pts with mMCC were treated with ICIs. Pt characteristics are summarised in the table. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%); 10 (44%) complete metabolic responses (CMR) and 4 (17%) partial metabolic responses (PMR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival (PFS) rate was 39%. Increased OR were seen in pts aged less than 75 (OR 8/10, 80% vs 46%), pts with normal baseline LDH (OR 5/7, 71% vs 50%), pts with an immune-related adverse event (irAE) (OR 6/6, 100% vs 47%) and in MCPyV negative pts (OR 11/16, 69% vs 43%). Pts with a CMR had lower mean-tumor volume on baseline FDG-PET scan (CMR: 35.7mL, no CMR: 187.8mL, p = 0.05). No correlation was seen between tumor PD-L1 positivity and response to ICI (p = 0.25) or MCPyV status (p = 0.76). Similarly, no association was seen between OR and CD3 staining within the tumor (p = 0.07). 10 pts received radiation (RT) during ICI: 4 pts started RT concurrently (OR 75%, CMR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. 6 pts (26%) had a Grade 1-2 irAE.

Baseline characteristics

Patient Characteristicsn = 23
Age (years) Median (range)75 (64 to 91)
Gender Male Female18 5
ECOG 0 12 38 12 3
ICI Avelumab Pembrolizumab Other (BGB-A317)15 5 3
MCPyV status Positive Negative7 16
Visceral disease17
Prior chemotherapy10
History of autoimmune disease2
Previous immunosuppression2

Conclusions

ICIs showed efficacy and safety consistent with trial data. Younger age, negative MCPyV status, normal LDH, lower baseline FDG-PET tumor volume and irAEs are potentially associated with enhanced response.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R.J. Hicks: Shareholder / Stockholder / Stock options: Telix Pharmaceuticals; Travel / Accommodation / Expenses: Endocyte; Travel / Accommodation / Expenses: GE Medical Systems. R. Tothill: Honoraria (self), Travel / Accommodation / Expenses: Merck Serono. All other authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

342O - Response of nivolumab monotherapy in 124 Japanese patients with advanced melanoma: Interim analysis of prospective observational study (CREATIVE study)

Presentation Number
342O
Lecture Time
02:42 PM - 02:54 PM
Speakers
  • Naoya Yamazaki
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Naoya Yamazaki
  • Akira Takahashi
  • Kenjiro Namikawa
  • Tatsuya Takenouchi
  • Yasuhiro Nakamura
  • Shigehisa Kitano
  • Tomonobu Fujita
  • Kazumi Kubota
  • Takeharu Yamanaka
  • Yutaka Kawakami

Abstract

Background

Anti-PD-1 antibody nivolumab has been approved for advanced melanoma in Japan. Although there have been clinical trial reports on nivolumab treatment for advanced melanoma, real-world data on the efficacy of nivolumab in an Asian patient cohort is still lacking. The aim of this study is to obtain real-world data on the efficacy of nivolumab in Japanese patients with advanced melanoma.

Methods

This prospective observational study was performed on unresectable or metastatic melanoma patients who were treated with nivolumab. Primary endpoints were response rate (RR), and overall survival (OS). The secondary endpoints were progression-free survival (PFS) and the immune-related adverse events (irAEs) ratio.

Results

In total, 124 patients from 22 institutions in Japan were enrolled between Dec. 2015 and Dec. 2017. Mucosal melanoma (34%) was the most frequent subtype in this study, followed by acral lentiginous melanoma (20%), nodular melanoma (15%), superficial spreading melanoma (13%). We observed complete response (CR) in 2 (2%), partial response (PR) in 21 (17%), stable disease (SD) in 27 (22%), and progressive disease (PD) in 59 patients (47.6%) (objective RR: 19%). Use of nivolumab as first-line treatment showed a tendency toward higher response than when used as second-line treatment (objective RR, 23% vs 11%, P = 0.12). IrAEs comprised skin reactions and endocrine-related adverse effects. The median PFS in patients with skin reactions (or skin-related irAEs) was 8.61 months compared to 2.14 months without skin-related irAEs, and 8.99 months (p < 0.001) with endocrine function suppression compared to 2.14 months in the absence of endocrine-related irAEs.

Conclusions

The results of this interim analysis showed a lower RR than that reported in recent phase 2 trials conducted in Japan. The differences in the proportions of melanoma subtypes, with a higher proportion of mucosal and acral melanoma, and use of nivolumab as second-line treatment will probably lead to a lower RR to nivolumab in Japan. As the results of this study showed that the occurrence of irAEs had a significant impact on therapeutic efficiency, it is critical to take appropriate measures to manage the occurrence of irAEs.

Legal entity responsible for the study

The authors.

Funding

This study was sponsored by Public Health Research Foundation under the funding support from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb K.K.

Disclosure

N. Yamazaki: Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: ONO Phamaceuticals; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Novartis Pharma K.K.; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: MSD K.K.; Honoraria (self), Honoraria (institution): Merck Serono Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd. K. Namikawa: Honoraria (institution): Public Health Research Foundation; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme. T. Takenouchi: Advisory / Consultancy: Ono Pharmaceutical Co., Ltd.; Advisory / Consultancy: MSD KK; Advisory / Consultancy: Chugai Pharmaceutical Co., LTD.; Advisory / Consultancy: Novartis Pharma KK. Y. Nakamura: Honoraria (self): ONO pharmaceuticals; Honoraria (self): MSD; Honoraria (self): Bristol Myers-Squibb; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Taisho Toyama Pharma; Honoraria (self): Maruho; Honoraria (self): Taiho Pharma. S. Kitano: Honoraria (self): AstraZeneca; Honoraria (self): Chugai; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Nippon Kayaku; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Meiji Seika Pharma; Honoraria (self): Taiho. T. Fujita: Honoraria (self): Public Health Research Foundation; Advisory / Consultancy: ONO PHARMACEUTICAL CO., LTD; Advisory / Consultancy: Bristol-Myers Squibb Company. T. Yamanaka: Honoraria (self), Honoraria (institution): Takeda; Honoraria (self), Honoraria (institution): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai. Y. Kawakami: Advisory / Consultancy: Public Health Research Foundation; Advisory / Consultancy: Ono Pharmaceutical Co., LTD; Advisory / Consultancy: Bristol-Myers Squibb Company. All other authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

Invited Discussant 341O and 342O

Lecture Time
02:54 PM - 03:06 PM
Speakers
  • Mohamad Farid Harunal Rashid
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Mohamad Farid Harunal Rashid
Mixed session - Melanoma Mixed Proffered paper and Mini oral session

343O - Global patterns in the incidence of acral melanoma: Systematic review and meta-analysis

Presentation Number
343O
Lecture Time
03:06 PM - 03:16 PM
Speakers
  • Kenneth K. Cho
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Kenneth K. Cho
  • Anne E. Cust
  • Yun Megan Foo
  • Guy Eslick

Abstract

Background

Although most cutaneous melanomas occur on sun-exposed skin, melanomas can also arise on sun-shielded skin including the palms, soles and subungual areas. These are categorized by their anatomical location as acral melanoma (AM). The global incidence of CM has increased considerably in recent decades, however little is known about the global incidence of AM. A meta-analysis was performed to explore the global incidence of AM, in particular examining the location of AM in the palms, soles and nails.

Methods

A systematic review was carried out using five electronic databases from their inception to June 2019, identifying all studies that reported the incidence of AM. Data were independently extracted by two investigators. Study quality was assessed using the appraisal tool for Cross-Sectional Studies (AXIS), the Joanna Briggs Institute (JBI) 2017 Critical Appraisal Checklist for Case Series, and the Newcastle-Ottawa Scale for the case control and cohort studies. We used a Random-effects model for data analysis based on event rates (ER) and 95% confidence interval (CI).

Results

From the 165 studies included, the results of 2,668,701 patients with melanoma were analyzed. AM was more likely to affect females ER: 53% (95% CI 49%-56%, I2 = 56.95% p = 0.14), and more often present on the soles ER: 73% (95% CI 66%-78%, I2 = 76.47% p < 0.001) compared to the palms ER: 5% (95% CI 4%-7%, I2 = 0.00% p < 0.001), lower nails ER: 20% (95% CI 15%-28%, I2 = 87.92% p < 0.001) and upper nails ER: 24% (95% CI 16%-35%, I2 = 93.30% p < 0.001). During the presentation association between ethnicity and geography with AM will also be explored.

Conclusions

AM affected the soles of the feet more often than any other location.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

344O - Metastatic acral melanoma treatment outcomes: A systematic review and meta-analysis

Presentation Number
344O
Lecture Time
03:16 PM - 03:26 PM
Speakers
  • Kenneth K. Cho
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Kenneth K. Cho
  • Anne E. Cust
  • Yun Megan Foo
  • Guy Eslick

Abstract

Background

Melanomas that typically arise on sun-shielded skin are classified their anatomical location as acral melanoma (AM). These rare melanomas more commonly affect patients of Asian background, and have different aetiological mechanisms and somatic mutation signatures compared to other cutaneous melanomas. The treatment response of systemic therapy for AM is unclear. The current study systematically reviewed and meta-analysed the existing data in the literature regarding the treatment response of AM.

Methods

Five electronic databases were systematically searched from their inception to June 2019, identifying all studies that reported treatment responses of metastatic AM and ALM. Data were independently extracted by two investigators according to predefined clinical endpoints. We used a Random-effects model for data analysis based on event rates (ER) and 95% confidence interval (CI).

Results

Ten studies, with 215 patients, met the inclusion criteria for the meta-analysis. Average complete response probabilities were ER: 9% (95% CI 4%-18%, I2 = 0.00% p < 0.001), partial response ER: 19% (95% CI 12%-29%, I2 = 0.00% p < 0.001), stable disease ER: 35% (95% CI 20%-54%, I2 = 51.94% p = 0.1) and progression of disease ER: 42% (95% CI 26%-59%, I2 = 45.36% p 0.34). Subgroup analysis of patients receiving immunotherapy compared to chronic sun damaged skin and mucosal melanoma will be presented.

Conclusions

Overall patients with metastatic acral melanoma had significant rates of treatment response to systemic therapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

Invited Discussant 343O and 344O

Lecture Time
03:26 PM - 03:38 PM
Speakers
  • Lu Si
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Lu Si
Mixed session - Melanoma Mixed Proffered paper and Mini oral session

345O - Melanomas and stress patterns on the plantar surface of the foot: A systematic review and meta-analysis

Presentation Number
345O
Lecture Time
03:38 PM - 03:43 PM
Speakers
  • Yun Megan Foo
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Yun Megan Foo
  • Kenneth K. Cho
  • Anne E. Cust
  • Guy Eslick

Abstract

Background

UV light exposure is a recognized causative factor in cutaneous melanoma. However melanomas can emerge in sun-shielded areas of the skin such as the plantar surfaces, and the pathogenesis of these melanomas are largely unknown. One hypothesis is that repetitive mechanical stress leads to the formation of melanoma on the plantar and subungual surfaces. We performed a systematic review and meta-analysis to investigate the link between shear stress and plantar melanoma.

Methods

Five electronic databases were systematically searched from their inception to June 2019, in order to identify all studies which explored stress patterns of the foot and melanoma. The data was extracted by two reviewers, and the study quality assessed through the appraisal tool for Cross-Sectional Studies (AXIS), the Joanna Briggs Institute (JBI) 2017 Critical Appraisal Checklist for Case Series, and the Newcastle-Ottawa Scale for cohort studies. Studies which included images of the melanoma sites on the foot were digitally merged to create “foot maps” of the pooled plantar melanoma locations. We used a random-effects model for data analysis based on event rates (ER) and 95% confidence interval (CI).

Results

Seventeen studies with a total of 1,200 patients were included in the meta-analysis. Plantar melanomas were most often found in the hindfoot ER: 50% (95% CI 42%-57%, I2 = 72.06% p = 0.97), followed by the forefoot ER: 27% (95% CI 23%-31%, I2 = 0.00% p < 0.001) and midfoot ER: 20% (95% CI 15%-26%, I2 = 59.58% p < 0.001). The digitally merged foot maps corresponded with mechanical stress points on the plantar surface of the foot. With the subungual melanomas, melanomas disproportionally affected the nail of the hallux even after accounting for surface area ER: 77% (95% CI 68%-84%, I2 = 65.22% p < 0.001).

Conclusions

Melanomas of the plantar foot disproportionally affected the hind foot and weight bearing areas, whilst subungual melanomas had a predilection towards the hallux. These findings suggest mechanical stress may increase the risk of melanomas in the plantar and subungual areas.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

346O - Association of BAP1 with ATR protein and their clinical significance with patient outcome in uveal melanoma

Presentation Number
346O
Lecture Time
03:43 PM - 03:48 PM
Speakers
  • JAYANTI JHA
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • JAYANTI JHA
  • Neelam Pushker
  • Mithalesh K. Singh
  • Lata Singh
  • Seema Sen
  • Jasbir Kaur
  • Seema Kashyap

Abstract

Background

Uveal melanoma (UM) is an intraocular malignancy commonly arising from the choroid. There is a lack of effective therapy to detect and treat early metastatic spread in these patients. Therefore, it is important to find new biomarkers that help in early detection of metastasis. ATR is localized at position 23 on the same chromosome 3 where BAP1 is located at position 21.1. Loss of BAP1 is a known poor prognostic marker of uveal melanoma. There is no current study available on UM with respect to ATR protein that induces DNA damage response. Therefore, the aim of the study is to detect the expression of ATR protein in the UM patients and correlate its expression with BAP1 loss.

Methods

Expression of nuclear ATR was investigated on sixty-nine UM patients which were divided into two groups on the basis of BAP1 expression. Formalin-fixed paraffin embedded choroidal melanoma samples were taken to evaluate the expression of ATM and BAP1 by immunohistochemistry and validated by semi-quantitative PCR. Results were then correlated with clinicopathological parameters. To determine the prognostic significance, Kaplan–Meier and multivariate analysis were performed.

Results

Patients with BAP1 loss also showed ATR loss in 62% of the cases which was statistically significant with high tumor pigmentation, LTD >10mm and cell type. At transcription level, down-regulation of ATR gene was found in 45% of cases and these results were in line with the IHC results. On multivariate analysis, advanced tumor staging and loss of ATR protein found to be independent prognostic factors.

Conclusions

Our study emphasized the fact that loss of ATR could be a potential biomarker to detect the early metastasis in uveal melanoma. Hence, it could have a key role for therapeutic purpose. However, further studies are required in a larger cohort of patients with longer follow up and translational validation needs to be performed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

Discussion led by moderators

Lecture Time
03:48 PM - 03:58 PM
Speakers
  • Caroline Robert
  • Paul Lorigan
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Caroline Robert
  • Paul Lorigan