Abstract 381P
Background
The choice of the correct therapeutical strategy in BR and LA PDAC is still demanding. The dynamic of cftDNA of KRAS represents an important biomarker in radically resected and metastatic diseases.
Methods
We prospectively collected plasma samples (3 mL) for each PDAC at 2 timepoints: before chemotherapy start (T0) and at the first radiological evaluation (T1); the cftDNA was extracted and analyzed for KRAS mutations (mutKRAS) at codons 12 and 13 by multiplex assay using digital PCR. We aimed to assess the frequency and clearance of mutKRAS in BR and LA PDAC patients at T0 and T1, to compare the difference in T0 to a control cohort of metastatic patients and to evaluate their impact on overall survival (OS).
Results
A total of 54 patients with PDAC treated at Pisa University Hospital were included; of them, 14 (25.9%) patients had BR and 13 (24.1%) had LA disease, while 27 (50%) belonged to the control cohort of metastatic patients. There was no statistically significant difference in terms of frequency of mutKRAS at T0 between the two cohorts, respectively 70.4% for metastatic and 48.1% for BR/LA (p>0.05), however, at the same timepoint the first one had a significant higher number of mutKRAS copies/mL (p=0.001). In BR/LA, at T1, mutKRAS became undetectable (mut(-)KRAS) in 10 patients (62.5%). On 31st March 2024, 19 out of 27 patients had died; patients with mut(-)KRAS cftDNA at T1 had a significantly longer median OS (mOS) compared to mut(+)KRAS ones (29.9 vs 15.0 months, p=0.002). Moreover, we found a statistically significant difference in mOS in mut(+)KRAS turned to mut(-)KRAS cftDNA vs the ones who did not (32.6 vs 15.0 months, p=0.013). Among other clinical factors, surgery (p=0.009) and BR stage at diagnosis (p=0.01) affected mOS. At a multivariate analysis for mOS none of the abovementioned factors demonstrated an independent prognostic role.
Conclusions
Our limited series confirms that the evaluation of mut KRAS cftDNA is feasible in LA/BR PDAC patients; its role in this setting is still challenging and further analyses in a larger population are needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Fornaro: Financial Interests, Personal, Invited Speaker: Lilly, MSD, Servier, Incyte, BMS GmbH & Co KG; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca/Daiichi Sankyo, Servier, Incyte, Taiho Pharmaceutical, Lilly, Astellas Pharma; Financial Interests, Institutional, Funding: Merck Sharp & Dohme, Astellas Pharma, Incyte, Janssen, Nucana, Daiichi Sankyo/AstraZeneca, Roche, BeiGene, BMS GmbH & Co KG, AstraZeneca. G. Masi: Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai, MSD Oncology, Roche; Financial Interests, Institutional, Funding: Terumo. R. Danesi: Financial Interests, Personal, Advisory Board: Ipsen, Novartis, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Eusa Pharma. M. Del Re: Financial Interests, Personal, Invited Speaker: Astellas, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis, Roche, MSD, Lilly, Ipsen; Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Ipsen, Janssen, Sanofi-Aventis, Amgen. C. Vivaldi: Financial Interests, Personal, Advisory Board: AstraZeneca, Taiho; Financial Interests, Personal, Invited Speaker: Terumo, Servier, MSD, AstraZeneca, Roche. All other authors have declared no conflicts of interest.