Abstract 3120
Background
Immune-checkpoint inhibitors have revolutionized advanced melanoma care. Despite major improvements in survival, many patients do not derive long-term benefit and treatment could cause severe side-effects. Since several new (combination) therapies are or will become available, early prediction of non-responsiveness (NR) to anti-PD-1 monotherapy becomes relevant in order to enable early switch to next line (combination) treatment and avoid nonsensical care.
Methods
Advanced melanoma patients treated with pembrolizumab (PEM) who started PEM between June 2014 and August 2016 were included in this retrospective analysis. S100 and lactate dehydrogenase (LDH) levels were routinely determined prior to initiation of PEM and every 3-weeks during treatment. NR to treatment was defined as progressive disease or death at 6 months after start of PEM. Biomarker response characteristic (BReC) plots were obtained and LDH and S100 response cut-offs were determined based on two criteria: specificity for NR > 95% and feasibility to use in clinical practice. Next, sensitivity, specificity and predictive values were generated per follow-up time point (week 3, 6, 9, 12 and 15).
Results
166 advanced melanoma patients were included. The BReC analyses showed clear relations between an early (week 3 to 15) increase in tumor biomarker and NR. An increase of > 50% in LDH or a > 100% increase in S100 above the upper limit of normal compared to baseline at any follow-up interval was determined as criterion to positively test for NR. Obtained specificity ranged from 0.97-0.98 and the positive predictive value ranged from 0.92-0.96 for the studied follow-up intervals. Obtained sensitivity for detecting non-responsiveness ranged from 0.25 (95% CI; 0.16-0.35) at 3 weeks of follow-up to 0.35 (95% CI; 0.24-0.47) at 12 weeks of follow-up.
Conclusions
An early increase in S100 and/or LDH are strong parameters for non-responsiveness to PD-1 blockade in advanced melanoma. Prospective confirmation is needed before clinical implementation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Netherlands Cancer Institute.
Disclosure
E.A. Rozeman: Travel / Accommodation / Expenses: NanoString; Travel / Accommodation / Expenses: MSD. J.V. van Thienen: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. J.B.A.G. Haanen: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AZ/MedImmune; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Immunocore; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: Celsius; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Gadet. C.U. Blank: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly ; Advisory / Consultancy: GSK; Advisory / Consultancy: GenMab; Research grant / Funding (institution): NanoString; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.
Resources from the same session
5579 - Quality of informed consent in clinical trials patients
Presenter: Gianluca Catania
Session: Poster Display session 3
Resources:
Abstract
5147 - Patient's rights: Where do we stand?
Presenter: Maja Kozuh
Session: Poster Display session 3
Resources:
Abstract
1279 - The oncology nurse coordinator’s role in a digestive oncology department: Impact on patient and hospital
Presenter: Fouad Awada
Session: Poster Display session 3
Resources:
Abstract
1670 - Nursing model for a breast cancer unit at the Catalan Institute of Oncology
Presenter: Ana Rodriguez-ortega
Session: Poster Display session 3
Resources:
Abstract
3936 - Role of cancer nurse in the prevention and control of acute deterioration for oncohematologic patient
Presenter: Raquel Azor Portolés
Session: Poster Display session 3
Resources:
Abstract
2789 - Standardized nursing care in the department of radiotherapy of a network of cancer centres
Presenter: José Delgado
Session: Poster Display session 3
Resources:
Abstract
4482 - Exploring anxiety, depression and quality of life of ambulatory cancer patients during chemotherapy.
Presenter: Theodoula Adamakidou
Session: Poster Display session 3
Resources:
Abstract
3075 - Implementing a Cancer Survivorship Program for Individuals with Recurrent Breast Cancer
Presenter: Darcy Burbage
Session: Poster Display session 3
Resources:
Abstract
3869 - The perceptions of parents/guardians regarding their child/adolescent’s experience of reflexology or non-specific foot massage The perceptions of parents/guardians regarding their child/adolescents experience of reflexology or non-specific foot massage
Presenter: Patricia Fox
Session: Poster Display session 3
Resources:
Abstract
4064 - Quality of life in survivors of adult haematological malignancies
Presenter: Anita Immanuel
Session: Poster Display session 3
Resources:
Abstract