Abstract 1500P
Background
Neoadjuvant treatment with immune checkpoint inhibitors (ICI) induces high pathologic response rates with prolonged relapse-free survival. A subset of patients (pts), however, do not respond, which necessitates new additional treatments. Domatinostat (DOM) inhibits pathways relevant for proliferation, differentiation, and metastasis of tumor cells, and preclinical models show promising results when combined with ICI. As a secondary study of the DONIMI trial, we evaluated health-related quality of life (HRQoL) in pts with stage III cutaneous or unknown primary melanoma and high interferon-gamma (IFN-γ) signature (sig).
Methods
Pts were randomly assigned to receive either nivolumab (NIVO, arm A) or NIVO+DOM (arm B). HRQoL was evaluated in both arms over the course of 6 weeks of treatment prior to surgery, and assessed with the European Organisation for Research and Treatment of Cancer QoL questionnaire-C30 (EORTC QLQ-C30) and a 19-item immunotherapy-related symptom checklist from the EORTC item bank. Baseline to follow-up (FU) analyses were used to assess the difference in HRQoL outcomes between arm A and arm B. Differences were adjusted for age, sex, and FU.
Results
In total 20 pts were included in the analyses (arm A n=10; arm B n=10). Questionnaire completion rates were 90% at baseline and 100% at 6 weeks FU. Median age of arm A was 61 years (range 33 – 81) versus 55 (range 36 – 69) years in arm B. Compared to arm A, arm B pts scored significantly lower on the QLQ-C30 summary score, encouraging us to look closer to other subscales. Arm B pts reported lower emotional, cognitive, role, and social functioning, and global health, and higher symptom burden of fatigue and pain than arm A pts. Differences in mean change were statistically significant (p<0.05) and varied from subtle to unequivocal clinical relevance. Arm B pts reported symptoms like itching, joint and muscle pain, and physical exhaustion more frequently than arm A pts.
Conclusions
While all patients were eligible for resection without delay, results suggest that stage III melanoma pts with a high IFN-γ sig treated with neoadjuvant ICI and DOM are more likely to suffer from treatment-related symptoms than pts treated with ICI only.
Clinical trial identification
NL70859.031.19.
Editorial acknowledgement
Legal entity responsible for the study
Dutch Cancer Institute (NKI).
Funding
Antoni van Leeuwenhoek hospital is the sponsor, 4SC the subsidising party.
Disclosure
A.M. Menzies: Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Institutional, Advisory Board: Pierre Fabre; Non-Financial Interests, Institutional, Advisory Board: QBiotics. R.P.M. Saw: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: QBiotics. A.J. Spillane: Non-Financial Interests, Institutional, Advisory Board: QBiotics; Financial Interests, Institutional, Funding: Stryker. B.A. van de Wiel: Non-Financial Interests, Institutional, Advisory Board: BMS. R.A. Scolyer: Financial Interests, Institutional, Funding: QBiotics; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Funding: NeraCare; Financial Interests, Institutional, Funding: Amgen inc.; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Myriad Genetics; Financial Interests, Institutional, Funding: GSK. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Merck Pfizer; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Sirius Medical; Financial Interests, Institutional, Advisory Board: 4SC; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Merck Pfizer. G.V. Long: Non-Financial Interests, Institutional, Advisory Role: Aduro Biotech Inc; Non-Financial Interests, Institutional, Advisory Role: Amgen inc.; Non-Financial Interests, Institutional, Advisory Role: Array Biopharma inc.; Non-Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim International GmbH; Non-Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Non-Financial Interests, Institutional, Advisory Role: Highlight Therapeutics S.L.; Non-Financial Interests, Institutional, Advisory Role: Merck Sharpe & Dohme; Non-Financial Interests, Institutional, Advisory Role: Novartis Pharma AG; Non-Financial Interests, Institutional, Advisory Role: Pierre Fabre; Non-Financial Interests, Institutional, Advisory Role: QBiotics Group Limited; Non-Financial Interests, Institutional, Advisory Role: Regeneron Pharmaceuticals inc. C.U. Blank: Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: GSK; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: GenMab; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Third Rock Ventures; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: NanoString; Financial Interests, Personal, Stocks/Shares, Co-founder: Immagene BV. A.H. Boekhout: Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.