Targeted treatments extend survival in pancreatic cancer
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A precision medicine approach to therapy significantly extended survival for patients with pancreatic cancer compared with standard chemotherapy, according to results of a retrospective study published in The Lancet Oncology.
The findings suggest that molecularly guided treatments that target oncogenic drivers and the DNA damage response and repair pathway deserve further prospective study, researchers wrote.
“[Pancreatic cancer] is a notoriously difficult disease to treat, and many of the promising therapies, including immunotherapy, have not yet made any impact on most patients with pancreatic cancer,” Michael Pishvaian, MD, PhD, associate professor in the department of oncology and director of the gastrointestinal, developmental therapeutics and clinical research programs at Kimmel Cancer Center at Sibley Memorial Hospital and Johns Hopkins University School of Medicine, told Healio. “There is [also] no question that pancreatic cancer research is underfunded, especially given that it is projected to be the second leading cause of cancer-related death in the next few years.”
About 25% of pancreatic cancers have actionable molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy, according to study background.
The Pancreatic Cancer Action Network’s Know Your Tumor (KYT) program enables patients with pancreatic cancer from throughout the United States to undergo multi-omic profiling to provide molecular tailored therapy options and clinical trial recommendations.
Pishvaian and colleagues retrospectively analyzed 1,856 patients referred to the KYT program to determine whether molecularly matched therapy prolonged OS compared with unmatched therapy.
Median OS from diagnosis of advanced disease until death served as the study’s primary endpoint.
Researchers identified actionable molecular alterations in 282 (26%) of 1,082 biopsy samples from patients registered in the KYT program who underwent molecular testing. Among 677 patients with available outcomes, 189 had actionable molecular alterations.
Median follow-up was 383 days (interquartile range, 214-588).
Results showed patients with actionable molecular alterations who received matched therapies (n = 46) achieved significantly longer median OS than patients who received unmatched therapies (n = 143; 2.58 years vs. 1.51 years; HR = 0.42; 95% CI, 0.26-0.68).
The matched-therapy recipients also achieved longer OS than 488 patients who did not have actionable molecular alterations (2.58 years vs. 1.32 years; HR = 0.34; 95% CI, 0.22-0.53).
Researchers reported no significant difference in median OS between patients who received unmatched therapy and those without an actionable molecular alteration (HR = 0.82; 95% CI, 0.64-1.04).
“The ability of patients with pancreatic cancer to undergo tumor molecular profiling or receive targeted therapies is a challenge in the U.S. health care system and — although about 25% of them have actionable alterations — less than 5% are able to receive targeted therapies because of either the aggressiveness of the disease or logistical and economic issues,” Pishvaian and colleagues wrote. “However, our results show that patients who have actionable molecular alterations can derive considerable benefit from receiving a matched therapy.”
Although the study had a small and highly selected population of patients, it serves as an encouraging starting point for a structured investigation of molecularly matched therapies, Jörg Kleeff, MD, FACS, professor and chair of visceral surgery at Martin Luther University Halle-Wittenberg in Germany, and Christoph W. Michalski, MD, clinical researcher in the department of general, visceral and transplantation surgery at Heidelberg University, wrote in an accompanying editorial.
However, important questions have yet to be addressed, they added.
“These questions comprise not only technical details regarding the genome sequencing of tumor tissues and of germline material but also clinical questions, such as timing of treatment and choice of the right chemotherapy, as well as identification of appropriate combination treatment regimens,” they wrote. “If molecularly matched treatment is going to be used as a first-line therapy, the biopsy, sequencing and bioinformatics analysis platform will need to provide results within a short time frame.” – by John DeRosier
Disclosures:
Pishvaian reports consultant/advisory roles with AstraZeneca, Caris Life Sciences, Celgene, Halozyme, Merck, Merrimack, Perthera and Sirtex Medical, and institutional research funding from ARMO Biosciences, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Calithera Biosciences, Celgene, Celldex, Curegenix, Fibrogen, Genentech, Gilead Sciences, GlaxoSmithKline, Halozyme, Karyopharm Therapeutics, MedImmune, Merck, Novartis, Regeneron, Pfizer, Pharmacyclics and Tesaro. Please see the study for all other authors’ relevant financial disclosures. Kleeff and Michalski report no relevant financial disclosures.
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