Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Pancreatic cancer patients who receive treatments targeting their actionable molecular mutations have the best outcome, demonstrate results from the Know Your Tumor programme in the USA.
“These real-world outcomes suggest that the adoption of precision medicine can have a substantial effect on survival in patients with pancreatic cancer, and that molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway warrant further prospective evaluation”, say lead author Michael Pishvaian from The University of Texas MD Anderson Cancer Center in Houston, USA, and team.
The registry includes data for 1856 patients who enrolled in the programme between 2014 and 2019, and underwent molecular testing for pathogenic variants in a raft of DNA damage response and repair (DDR) genes, as well as high microsatellite instability.
Of the 1082 patients who received a personalised report of their test results, 26% had a mutation linked to benefits for a specific treatment. The final analysis included 677 patients with available outcome data, 189 of whom had an actionable mutation, who were followed up for a median of 383 days, the researchers explain in The Lancet Oncology.
The 46 patients with an actionable mutation who received the matching targeted therapy had longer overall survival (OS) than the 143 patients who had an actionable mutation but were given only unmatched treatments, at a median of 2.58 versus 1.51 years and a significant hazard ratio (HR) for death of 0.42.
These 46 patients also had significantly longer OS than the 488 patients without any actionable mutation, who survived for a median of 1.32 years, giving a significant HR of 0.34, whereas patients with an actionable mutation given an unmatched therapy had comparable OS to those without any actionable mutations.
And a similar pattern was found when assessing only the 94 patients with a DDR pathway mutation, with a median OS of 3.81 years for 27 patients treated with a PARP or ATR inhibitor versus 1.71 years for the 67 patients who did not receive this matched therapy, giving a HR for death of 0.48.
This was also true for the 95 patients with non-DDR actionable mutations, with significantly longer OS for the 19 patients given a matched therapy, at a median of 2.39 years versus 1.31 years for the 76 patients given other forms of treatment (HR=0.40).
“We showed that the median overall survival of patients with advanced pancreatic cancer who had actionable alterations receiving matched therapy is 1 year longer than those with actionable alterations receiving unmatched therapy, or those without actionable alterations”, write Michael Pishvaian et al.
Emphasizing that “[n]o other therapeutic modality has offered an advantage of this magnitude to this patient population”, they believe that “these findings set the stage for prospective clinical trials guided by molecular profiling.”
The authors of an accompanying comment describe the OS findings as “striking” and “important in that they define an estimation of the current number of potentially actionable targets”, but say the results also “provide a–rather disappointing–real-world assessment of the number of patients who actually receive molecularly targeted treatment”.
Nevertheless Jorg Kleeff and Christoph Michalski, both from Martin-Luther University Halle-Wittenberg in Germany, agree the research is an “encouraging starting point” for answering “important questions” on the use of molecularly matched therapies, such as the optimal testing protocols, the timing of such treatment, especially among patients with resectable or borderline-resectable disease, and the choice of backbone chemotherapy.
Pishvaian MJ, Blais EM, Brody JR, et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol; Advance online publication 2 March 2020. https://doi.org/10.1016/S1470-2045(20)30074-7
Kleeff J, Michalski CW. Precision oncology for pancreatic cancer in real-world settings. Lancet Oncol; Advance online publication 2 March 2020. https://doi.org/10.1016/S1470-2045(20)30148-0
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