1758P - Body composition meets precision medicine: The prognostic value of sarcopenia in patients (pt) treated with Molecularly Targeted Agents (MTA)

Background

Sarcopenia is associated with worse prognosis in pt treated with chemo (CT) or immunotherapy, yet there is scarce information with MTA. Some gene mutations (mut) have been involved in muscle wasting pathogenesis but remains unclear which molecular mediators can alter body composition. Our study aimed to analyze the association between sarcopenia and clinical outcomes in MTA-treated pt and to explore the tumor genomic landscape.

Methods

Retrospective analysis of metastatic solid tumors treated with MTA within the spEcial Medication (ME) program at the Catalan Institute of Oncology (off-label or expanded access use) between Jan’11-Dec’19. Skeletal mass index (SMI) was assessed at L3 landmark in computed tomography scans performed one month before first MTA dose. SMI was dichotomized according to the median [high (H) vs low (L) SMI]. Histology-oriented single analysis assays were performed according to the prevalence of actionable findings (IHC, FISH or PCR).

Results

We included 167 cases: 56% female, 86% <75 years, 84% ECOG <2 and 79% received <3 lines of treatment. Locations were thoracic (33%), breast (15%), sarcoma (15%), gastrointestinal (14%), gynae (9%), genitourinary (7%) and others (7%). Oncogenic drivers that guided matched MTA were found in 97 tumors: 75% received MTA monotherapy and 25% combinations (CT or other MTA). Globally there were 28% cases with HER2 overexpression (ove), ALK (23%)/MET (1%)/ROS1 (1%) fusions and EGFR (19%)/BRAF (11%)/BRCA1/2 (7%)/KRAS (4%) mut. Overall survival (OS) was 21.8 months (m) in H-SMI/driver, 13.9 m in H-SMI/no-driver, 10.8 m in L-SMI/driver and 9 m in L-SMI/no-driver groups (p=0.0037). Of note, OS rate at 12 m was 65% (CI 95%; 53-81) in H-SMI/driver group compared to 38% (CI 95%; 24-59) in L-SMI/no-driver group. Interestingly, 81% HER2ove cases had L-SMI (p=0.005).

Conclusions

Our exploratory study shows that pt with H-SMI and presence of an oncogenic driver have better survival outcomes, hence highlights the relevance of guaranteeing early access to MTA through ME programs. L-SMI in HER2ove pt warrants further confirmation and investigation of the underlying mechanism in muscle wasting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Societat Catalano-Balear d'Oncologia (SCBO-P2021 grant).

Disclosure

C. Hierro: Financial Interests, Personal, Invited Speaker: MSD, Lilly; Financial Interests, Personal, Research Grant, Principal Investigator of Merck Research Grant in Personalized Medicine 2020 : Merck; Non-Financial Interests, Principal Investigator, Clinical Trial: BMS, Zymeworks, ALX Oncology, AstraZeneca; Other, Other, Travel fees: BMS, Amgen, Roche, Merck. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer, Seagen; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Principal Investigator, Observational trial PI: Merck. All other authors have declared no conflicts of interest.