Abstract 1795P
Background
The use of immunotherapy to treat cancer patients can induce immune-related adverse events (irAEs) caused by non-specific activation of the immune system. Patient’s sex can influence adaptive immunity and, in turn, irAEs incidence, type and severity. We are undertaking a multicenter observational prospective study to investigate irAEs incidence, and female (F)/male (M) inequalities linked to sex (genetic and biological characteristics) and gender (psycho-social and behavioural determinants).
Methods
The study will recruit an equal number of F and M cancer patients undergoing immunotherapy treatments, followed for 12 months minimum. We record clinical and gender characteristics, irAEs, treatment response, recurrence and survival. We also collect biospecimens (blood and faecal samples) and use the extracted DNA or RNA to perform gene-expression, SNPs and microbiota analyses to identify the features associated with irAEs development.
Results
So far 111 patients were screened and 106 patients were included in the study. Patients’ age, cancer type, PS ECOG, and disease setting were well balanced in the two sex groups. irAEs (any type and grade - G) were 106 (46 patients), 41 F (23 G≥2) and 65 M (20 G≥2). Six-month cumulative incidence of G≥2 irAEs (95% confidence interval) was 61.4% (41.0-91.9%) in F and 27.9% (16.8-46.2%) in M patients (p=0.005); the difference was significant also at multivariable analysis adjusting for cancer type, PS ECOG, and setting (p=0.001). As regards gender characteristics, patients living alone, M in particular, are at higher risk of developing G≥2 irAEs vs those not living alone.
Conclusions
The study falls under the umbrella of “gender medicine”; it will define the sex/gender role in regard to irAEs incidence and will develop tools for individual irAEs prediction based on sex/gender determinants, and clinical and genetic/immunological/microbioma features. Based on the results, a personalized approach to immunotherapy administration can be implemented with positive impact on clinical management (irAE risk prediction could allow dosage adjustment or to treat irAEs early enough lowering the risk of treatment interruption) and healthcare system costs reduction.
Clinical trial identification
NCT04435964. ENCePP: EUPAS31282.
Editorial acknowledgement
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Funding
EU Horizon 2020 GA 741874.
Disclosure
G. Lo Russo: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. E. Verzoni: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Ipsen. J.P. Crown: Financial Interests, Personal, Full or part-time Employment: OncoMark; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Personal, Advisory Role: Novartis Ireland Ltd.; Financial Interests, Personal, Advisory Role: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AbbVie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis Ireland Ltd.; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: WO2020011770 (A1) - A method of predicting response to treatment in cancer patients; Financial Interests, Personal, Other, Stock and Other Ownership Interests: OncoMark; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Novartis Ireland Ltd.; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Puma Biotechnology. All other authors have declared no conflicts of interest.