Personalized medicine for advanced pancreas cancer: access to treatment according to molecular profile

Background

With a dramatic increase in incidence and a very poor prognosis, the pancreatic cancer‘s treatment remains a real challenge. We investigated here the feasibility and efficacy of personalized treatment according to molecular analysis in heavily pre-treated advanced pancreatic adenocarcinoma patients included in the ProfiLER protocol (NCT 02029001).

Methods

Between February 2013 and July 2015, 74 patients with metastatic pancreatic cancer were included in the ProfiLER trial. Tumor samples were analyzed for mutations/insertions/deletions and copy number variations using target high-throughput sequencing (NGS) and comparative genomic hybridization array (CGH). Blood samples were also collected. The patients, for whom an actionable alteration was identified, were treated according to their molecular profile.

Results

Tumor biopsy and archived tumor samples were collected from 74 patients and successfully analyzed in 45/74 (60.8%). Actionable molecular aberrations were identified in 22 patients (48.9%): 17 KRAS hotspot mutations, 2 CDKN2A homozygous deletions, 2 FGFR amplification (FGFR1/FGFR4), 1 ALK mutation, 1 HER2 amplification, 1 PI3KCA mutation and 1 MYC amplification. There was a median of 4.5 molecular aberrations per patient (range: 1–7). 14/22 tumor samples were issued from the primary site, 6 from distant metastases biopsy and 2 from fine needle aspiration. Low cellularity and insufficient DNA were the main reasons for molecular analysis failure. The median time between the patient's inclusion and the molecular tumor board patient presentation was 87.5 days [43-399]. To date, only 3 patients have been treated according to the molecular results, but unfortunately died. Most of participants were unable to be treated due to their worsening condition or further progression of their disease.

Conclusions

Identifying molecular targets in patients with metastatic pancreatic adenocarcinoma is feasible but forces clinicians and biologists to face very specific challenges due to the aggressive and rapidly fatal outcome of this disease. Molecular screening and accrual of patients in early-phase clinical trials have to be improved and anticipated.

Clinical trial identification

ProfiLER protocol: NCT 02029001; date: 28/11/2012

Legal entity responsible for the study

Pr Jean-Yves Blay

Funding

Le LYRIC (Lyon recherche intégrée en Cancerologie)

Disclosure

All authors have declared no conflicts of interest.