Abstract 39P
Background
Over 40% and 60% of patients (pts) with ALK-mNSCLC are alive and progression-free at 3 years with second (II)- and third (III)-generation (gen) aALK-TKIs. The side effects profile of aALK-TKIs is overall safe but their long-term effects in terms of BMC modifications are poorly studied. We conducted a retrospective analysis in this setting to study changes in multiparameter BMC.
Methods
BMC analysis was performed with a semiautomatic software to segment CT scans of the axial section passing through the midpoint of the vertebral body of L3. Specific tissues of interest radiodensities enable to identify and to quantify the skeletal muscle (SM) and total adipose tissue (TAT) composed of: visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT). Imaging was obtained before the initiation of each following line of aALK-TKIs.
Results
Between September 2015 and October 2023, 49 ALK-mNSCLC pts (M 20, F 29, median age 62) were sequentially treated. At baseline, 18% and 14% of pts had known dyslipidemia and mild obesity (BMI 25-38), respectively. First-line aALK-TKIs included crizotinib (C) (43%), alectinib (A) (55%), brigatinib (B) (2%). Nineteen progressing pts received second-line treatment with A (47%), ceritinib (CE) (16%) and lorlatinib (L) (37%) and third line treatment with B (50%) and L (50%) was given to 8 pts. Median progression-free survivals (PFS) were 22, 7 and 8 months with first-, second-and third-line TKIs, respectively. After I line treatment we observed a significant increase in VAT (+35.4%, p .003) and TAT (+15%, p .014) which maintains in following lines. This effect was larger with II gen aALK-TKIs for both VAT (p .007) and TAT (p .015) than with I gen TKIs. An association between baseline obesity or steroid use and TAT increase was also found (p .002 and p .003, respectively).
Conclusions
These preliminary results indicate that aALK-TKIs are associated with BMC changes in terms of adipose tissue disposition, in particular VAT. This effect occurs early at first-line treatment, is more pronounced with II gen TKIs and deserves further research to establish competing risks of comorbidity.
Legal entity responsible for the study
The authors.
Funding
University of Brescia.
Disclosure
S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers; Financial Interests, Institutional, Funding: Roche, AstraZeneca. All other authors have declared no conflicts of interest.