Abstract CT530: Multiorgan metabolic imaging response assessment of abemaciclib (MiMe-A): Oncodistinct 002

Abstract Background: Abemaciclib (A) activity against breast cancer as monotherapy or combined with endocrine therapy warrants further investigations in other cancer types. However, its significant toxicity profile illustrates the challenge of defining more precisely the patients unlikely to benefit from it, sparing them from useless toxicities. FDG-PET/CT can identify treatment-refractory disease with high negative predictive value, soon after the treatment onset and before morphological changes are observed. MiMe-A was built on the assumption that a therapy that does not induce tumoral metabolic changes 14 days after its onset is unlikely to achieve a significant clinical benefit. Methods: A multicenter phase II basket trial assessed the efficacy of A in 5 cancers types (cholangiocarcinoma, endometrial, urothelial carcinomas, oesophagal adeno- and squamous cell carcinomas). The primary endpoint is the ‘treatment success’, defined as metabolic response according to PERCIST at FDG-PET/CT performed during the first cycle (D14) and absence of disease progression per RECIST 1.1 after two cycles of A. A Simon’s 2-stage design was used in each cohort based on the null hypothesis that the treatment success rate will be ≤20%. An interim analysis for futility was performed on each cohort after accrual of 17 patients during the first stage. Results: The baseline characteristics and the metabolic and morphologic evaluation of eligible patients are shown below. *: stop treatment before the two months (due to progression or toxicities) IQR: interquartile range, PR: partial response, SD: stable disease, PD: progressive disease The treatment success rate was 0% for each cancer type except for urothelial carcinoma (5,9% (1/17 treatment success). Toxicities were mainly graded 1 or 2, including diarrhea, nausea, fatigue and haematological. Conclusion: A did not show significant anti-tumour activity in any of the five cohorts. But early metabolic response was noted in 29% of the oesophageal squamous cell carcinoma population, this finding did not translate in disease control at two months. This could be explained by an initial response rapidly followed by tumoral escape. A combination of A with other drugs should be explored in this cancer type. Esophageal adenocarcinomaN=17 Esophageal Squamous cell carcinomaN=17 CholangiocarcinomaN=17 Endometrial carcinomaN=17 Urothelial CarcinomaN=17 Baselinecharacteristics Age range 36-83 56-77 50-85 57-84 46-80 Median age (IQR) 65 (55-68) 67 (63-71) 70 (67-74) 68(64-73) 67 (63-71) Median number of lines of prior treatments (IQR) 3 (2-4) 3 (2-4) 2 (1-2) 3 (2-3) 3 (2-3) Metabolic response (PERCIST) assessment Complete metabolic response 0/17 0/17 0/17 0/17 0/17 Partial metabolic response 2/17 5/17 1/17 0/17 2/17 Stable metabolic disease 8/17 4/17 5/17 8/17 7/17 Progressive metabolic disease 4/17 7/17 9/17 6/17 4/17 Not evaluable 3/17 1/17 2/17 3/17 4/17 % Complete or partial metabolic response (95% CI) 12% (2%-36%) 29% (10%-56%) 6% (0%-29%) 0% (0%-20%) 12% (1%-36%) Response by RECIST (after 2 cycles) PR 1/17 1/17 0/17 0/17 0/17 SD 3/17 2/17 5/17 5/17 8/17 PD 6/17 10/17 7/17 9/17 8/17 Not available* 7/17 4/17 5/17 3/17 1/17 Citation Format: Laura Polastro, Nuria Kotecki, Diogo Martins-Branco, Diane Delaroche, Philippe Barthelemy, Stephane Holbrechts, Philippe Vergauwe, JC Goemine, Gauthier Demolin, Hans Prenen, Florian Clatot, Carlos Gomez Roca, Paulus Kristanto, Marianne Peasmans, Ahmad Awada, Alain hendlisz, Aurélien Carnot, Fransceco Sclafani, Philippe Aftimos. Multiorgan metabolic imaging response assessment of abemaciclib (MiMe-A): Oncodistinct 002 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT530.