Content Type: Article | Published March 2, 2020 (DOI: 10.1016/S1470-2045(20)30074-7) Copyright: © 2020 Elsevier Ltd. All rights reserved.
Michael J Pishvaian, MDa,b,† mpishvaian@mdanderson.org ∙ Edik M Blais, PhDb,† ∙ Prof Jonathan R Brody, PhDb,c ∙ Emily Lyons, BSd ∙ Patricia DeArbeloa, MDb ∙ Andrew Hendifar, MDe ∙ Sam Mikhail, MDf ∙ Vincent Chung, MDg ∙ Vaibhav Sahai, MDh ∙ Davendra P S Sohal, MDi ∙ Sara Bellakbira, BSb ∙ Dzung Thach, PhDb ∙ Lola Rahib, PhDd ∙ Subha Madhavan, PhDj ∙ Prof Lynn M Matrisian, PhDd ∙ Prof Emanuel F Petricoin, III, PhDb,k
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a)Department of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
b)Perthera, McLean, VA, USA
c) The Jefferson Pancreatic, Biliary, and Related Cancer Center and the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
d) The Pancreatic Cancer Action Network, Manhattan Beach, CA, USA
e) Cedars-Sinai Medical Center, Los Angeles, CA, USA
f) Mark Zangmeister Cancer Center, Columbus, OH, USA
g) City of Hope Cancer Center, Duarte, CA, USA
h) Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
i) Department of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA
j) Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA
k) Center for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, VA, USA
†) Contributed equally
SUMMARY
BACKGROUND:
About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whether patients with pancreatic cancer whose tumours harboured such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy.
METHODS:
In this retrospective analysis, treatment history and longitudinal survival outcomes were analysed in patients aged 18 years or older with biopsy-confirmed pancreatic cancer of any stage, enrolled in the KYT programme and who received molecular testing results. Since the timing of KYT enrolment varied for each patient, the primary outcome measurement of median overall survival was calculated from the initial diagnosis of advanced disease until death. We compared median overall survival in patients with actionable mutations who were treated with a matched therapy versus those who were not treated with a matched therapy
FINDINGS:
Of 1856 patients with pancreatic cancer who were referred to the KYT programme between June 16, 2014, and March 31, 2019, 1082 (58%) patients received personalised reports based on their molecular testing results. Actionable molecular alterations were identified in 282 (26%) of 1082 samples. Among 677 patients for whom outcomes were available, 189 had actionable molecular alterations. With a median follow-up of 383 days (IQR 214–588), those patients with actionable molecular alterations who received a matched therapy (n=46) had significantly longer median overall survival than did those patients who only received unmatched therapies (n=143; 2·58 years [95% CI 2·39 to not reached] vs 1·51 years [1·33–1·87]; hazard ratio 0·42 [95% CI 0·26–0·68], p=0·0004). The 46 patients who received a matched therapy also had significantly longer overall survival than the 488 patients who did not have an actionable molecular alteration (2·58 years [95% CI 2·39 to not reached] vs 1·32 years [1·25–1·47]; HR 0·34 [95% CI 0·22–0·53], p<0·0001). However, median overall survival did not differ between the patients who received unmatched therapy and those without an actionable molecular alteration (HR 0·82 [95% CI 0·64–1·04], p=0·10).
INTERPRETATION:
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.
FUNDING
Pancreatic Cancer Action Network and Perthera