Abstract 29P
Background
Peripheral conversion of thyroid hormones is key in regulating a wide range of functions, including central metabolism. Low fT3/fT4 ratio is a negative prognosticator in other cancers. Skeletal muscle index (SMI) calculated by CT scan at L3 level estimates commonly sarcopenia. Inflammation indexes (i.e., SII, SIRI, N/L) showed their prognostic values in CC. Correlation between those features and their independent contribution to prognosis of aCC is unclear. Cemiplimab is a new IO option in aCC.
Methods
135 aCC pts treated with cemiplimab at 12 centers from the MITO group were included. Data on fT3/fT4 were available for N=109 pts, 8 were excluded for thyroidal comorbidities. Of those, CBC values were available for 89 pts for calculating SII, SIRI and N/L. Baseline CT scans from 25 pts were available for SMI calculation. Pts characteristics resembled those reported by Tuninetti et al., EJC 2024. At first, variables were categorized as follows: ECOG PS: 0-1 vs 2, fT3/fT4 ratio, SII, SIRI and N/L: low vs high, (cut-off median) and SMI (sarcopenic vs not, cut-off 34 cm2/m2). Additional optimal cut-offs were explored by means of ROC analyses.
Results
at a mFUP of 6.9 mos, mPFS of ECOG PS 0-1 vs 2 was 4.5 vs 2.5 mos, HR 0.64; p=0.004, low vs high SII: 5.1 vs 2.7 mos, HR 0.53; p=0.019, low vs high fT3/fT4 ratio: 2.9 vs 5.3 mos, HR 1.44; p=0.150. mOS of ECOG PS 0-1 vs 2 was 15.8 vs 4.3 mos, HR 0.46; p<0.001, low vs high SII: NR vs 8.9 mos, HR 0.26; p=0.004, low vs high fT3/fT4 ratio: 8.9 mos vs NR, HR 2.95; p=0.008. At MV analyses, ECOG PS and fT3/fT4 ratio retained their prognostic impact (HR 0.50, p=0.002 and HR 3.13, p=0.011) while SII did not. SII values were higher in ECOG PS 2 vs 0-1, p=0.025. fT3/fT4 ratio as a continuous variable confirmed its prognostic value. No associations with other variables nor prognostic effects were found for SIRI, N/L or SMI, the latter limited by low numbers.
Conclusions
fT3/fT4 ratio, SII and ECOG PS predicted prognosis of aCC pts receiving cemiplimab. Independent impact on OS at MV analyses was found only for fT3/fT4 and ECOG PS, coherently with the finding that SII and PS are associated. These data provide new insights for valuable prognostic nomograms useful to optimize clinical use of innovative treatment in aCC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
V. Tuninetti: Financial Interests, Personal, Invited Speaker: MSD Oncology, GSK, Eisai; Financial Interests, Personal, Advisory Board: GSK, MSD, AstraZeneca. C. Pisano: Financial Interests, Personal, Advisory Board: MSD Oncology, GSK, AstraZeneca. M.C. Petrella: Financial Interests, Personal, Invited Speaker: MSD Oncology, GSK, AstraZeneca. V. Salutari: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Novocure, PharmaMar; Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure. S. Pignata: Financial Interests, Personal, Funding: AstraZeneca, GSK, MSD Oncology, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: MSD Oncology, AstraZeneca, Roche, GSK, Novartis, PharmaMar. G. Valabrega: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Eisai, MSD Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD Oncology. All other authors have declared no conflicts of interest.