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Precision medicine strategy in pancreatic ductal adenocarcinoma
A Tarabay1, L Swales2, C Smolenschi3
1Gustave Roussy, Département des soins de support, Villejuif, France.
Background:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited therapeutic options. Integration of molecular profiling may enable personalized treatment approaches. We evaluated the clinical utility of molecularly matched treatment (MMT) in a real-life cohort of PDAC patients.
Patients And Methods:
A retrospective chart review of clinical/molecular data was carried out, including all PDAC patients with a contributive molecular profile. Survival outcomes were compared across three groups: patients with actionable molecular alterations (MAs) who received MMT (MA/MMT), patients with actionable alterations without MMT (MA/No MMT), and patients without actionable alterations (No MA/No MMT).
Results:
Among 342 patients (median age 61 years; 48% female; 95% Eastern Cooperative Oncology Group 0-1), molecular profiling was carried out using tissue (50%), liquid biopsy (45%), or both (5%). The most common gene alterations were KRAS (84%), TP53 (72%), and CDKN2A (26%). Actionable alterations were found in 69 patients (20%), with 31 (45%) receiving MMT. Targeted therapies included notably olaparib (BRCA2), trastuzumab (HER2), and KRAS G12C inhibitors. Median overall survival (OS) from metastatic diagnosis was significantly longer in the MA/MMT group (32.9 months) compared with MA/No MMT (12.9 months) and No MA/No MMT groups (17.6 months) (P = 0.0008). From initial diagnosis, OS was 34.9, 27.1, and 21.5 months, respectively (P = 0.005). Median progression-free survival from MMT initiation was 5.5 months. The mean growth modulation index was 1.7 in the MA/MMT group versus 0.8 in the MA/No MMT group (P < 0.05). In variate analysis, MMT was correlated with improved OS [hazard ratio (HR) 0.51, P < 0.001 from metastasis; HR 0.59, P < 0.01 from diagnosis].
Conclusion:
To conclude, molecular profiling identified actionable alterations in 20% of PDAC patients. MMT was associated with a significant survival benefit, supporting molecular profiling into routine management, especially with the perspective of KRAS inhibitors.
