6O - Subcutaneous fat mass predicts progression-free survival in patients treated with antibody drug conjugates in early phase clinical trials

Background

Antibody drug conjugates (ADCs) have revolutionized the treatment of many solid tumours and hematological diseases. Little is known about the influence of body composition on efficacy and safety of ADCs.

Methods

All patients treated with ADCs in early phase clinical trials between 03/2015 and 03/2023 at Gustave Roussy were retrospectively included. A deep learning software (Anthropometer3DNet) automatically measured anthropometric parameters in 3D on pretreatment scans, allowing multi-slice measurements of muscle body mass (MBM), fat body mass (FBM), subcutaneous fat mass (SFM) and visceral fat mass (VFM). Other clinical and biological parameters were also retrieved. Primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results

A total of 136 patients were treated with ADCs most frequently for non-small cell lung cancers (56 patients, 41%) and colorectal cancers (31 patients, 23%). Median age, ECOG PS, albumin and number of previous lines of treatment were 60.8 years (30 to 85), 1, 42 g/L and 3 respectively. Median PFS and OS were 2.8 and 8.6 months respectively, 90 (66%) patients had experienced toxicity including 46 grade 3-4. The Royal Marsden Hospital (RMH) prognostic score > 1 was significantly associated with worse PFS (HR=2.13, p=0.007) and OS (HR=2.12, p=0.008). The number of treatment lines was significantly associated with worse OS (HR=1.21, p<0.001). SFM (HR=0.89, p=0.013) and FBM (HR=0.89, p=0.02) were significantly associated to PFS. Higher SFM (cutoff: 3.3 kg/m2) and FBM (cutoff: 3.6 kg/m2) were significantly associated with longer PFS (mPFS=3.8 vs 2.3 months and 3.7 vs 1.9 respectively) and numerically but non-significantly longer mOS (8.5 vs 7.7 months and 8.6 vs 6.4 months respectively). All anthropometric parameters were significantly associated with all-grade toxicity in the univariate but not in the multivariate analysis. None of them were associated with grade 3-4 toxicity.

Conclusions

In this large monocenter cohort, 3D measured high SFM and FBM were significantly associated with PFS. Automatic extraction of body composition parameters using AI may help in anticipating the benefits of ADCs in patients included in early phase clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.