Precision Oncology in Pancreatic Cancer: Experiences and Challenges of the CCCMunichLMU Molecular Tumor Board

Abstract

Background In pancreatic cancer, systemic treatment options in addition to chemotherapy remain scarce, and so far only a small proportion of patients benefit from targeted therapies. Objective The patients with pancreatic cancer discussed in the CCCMunich LMU Molecular Tumor Board were reviewed to gain a better real-world understanding of the challenges and chances of precision oncology in this hard-to-treat cancer. Methods Patients with pancreatic cancer who received comprehensive genomic profiling and were discussed in the interdisciplinary Molecular Tumor Board between May 2017 and July 2022 were included. These patients’ medical charts, comprehensive genomic profiling results, and Molecular Tumor Board recommendations were analyzed in this retrospective cohort study. Results Molecular profiles of 165 patients with pancreatic cancer were discussed in the Molecular Tumor Board. In the 149 cases where comprehensive genomic profiling was successful, KRAS mutations were detected in 87.9%, TP53 in 53.0%, and CDKN2A in 14.1%. 33.3% of KRAS wild-type patients harbored targetable mutations, while these were only found in 19.1% of patients with the KRAS mutation; however, this difference was not statistically significant. 63.8% of patients with successful testing received a targeted treatment recommendation by the Molecular Tumor Board; however, only 3.2% of these were put into practice. Compared to a historic cohort of patients with pancreatic cancer with synchronous metastatic disease diagnosed between 2010 and 2017, the patients from the pancreatic cancer cohort with synchronous metastatic disease had a longer survival. Conclusions This single-center experience emphasizes the challenges of targeted treatment in pancreatic cancer. Very few patients ultimately received the recommended therapies, highlighting the need for more and better targeted treatment options in pancreatic cancer, early comprehensive genomic profiling to allow sufficient time to put Molecular Tumor Board recommendations into practice, and close cooperation with clinical trial units to give patients access to otherwise not available targeted treatments.

Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer

“…Apart from the predominant subgroup of individuals with KRAS-mutated pancreatic cancer, focus has shifted to the KRAS wild-type population, particularly concerning molecularly guided treatments. KRAS wild-type pancreatic ductal adenocarcinoma accounts for approximately 10.7% to 12% of all PDAC cases, as reported by Philip et al (2022) and Dorman et al (2023) [35,36]. The findings have indicated that this subgroup exhibits an abundance of targetable alterations and includes a greater proportion of MSI-high and tumor mutational burden-high patients [35].…”

Implementing precision oncology for sarcoma patients: the CCCLMUmolecular tumor board experience

“…In contrast to other studies, the rate of therapeutic implementation in our cohort is high (31.3% of patients with actionable alterations). In other studies, MTB recommendations were followed through in 3–31.8% of patients with druggable alterations (Rodler et al 2021 ; Heinrich et al 2022 ; Dorman et al 2023 ; Gusho et al 2022 ; Sultova et al 2021 ; Horak et al 2021 ). Compared to the overall cohort, the ten patients treated according to their MTB recommendation were younger (mean 38 vs. 53 years) possibly indicating a selection bias toward patients with a good performance status.…”

“…In contrast, Rodler et al observed that genitourinary cancer patients were mainly included at primary presentation with metastatic disease (Rodler et al 2021 ). In pancreatic cancer, a cancer with a notoriously bad prognosis, Dorman et al observed a median time of 5.5 months between initial diagnosis and discussion in the MTB, owing to the fact that most patients with metastatic pancreatic cancer undergo tumor profiling at initial presentation (Dorman et al 2023 ). Regarding the dismal prognosis of BS/STS patients with metastatic disease, the long interval between initial diagnosis and discussion in the MTB raises the question whether comprehensive genomic profiling will positively impact the outcome of patients at later stages of their respective disease.…”

The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours

“…This corresponds with other findings that the MTB could improve treatment decisions and patient management. 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 …”