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Updated Guidelines Endorse Genomic Tests, Targeted Treatments for Metastatic Pancreatic Cancer

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Patients with metastatic pancreatic cancer should undergo germline and somatic testing to identify those who can benefit from targeted therapies, according to an updated guideline from the American Society of Clinical Oncology (ASCO).

The 2018 ASCO guideline focused on second-line therapy for patients who had experienced progression or intolerable toxicity after first-line therapy. The updated recommendations continue this focus based on added evidence for the PARP inhibitor olaparib as an option for maintenance therapy after first-line treatment, as well as new studies on treatment of tumors bearing fusions of the NTRK 1/2/3 genes.

Erin B. Kennedy of ASCO, in Alexandria, Virginia, and colleagues on an expert panel evaluated data from a randomized controlled trial of olaparib versus placebo, a report of phase-1 and -2 studies of larotrectinib, and a report on phase-1 and -2 studies of entrectinib as a basis for updating the advice for second-line therapy for metastatic pancreatic cancer.

Both larotrectinib and entrectinib target fusions of the NTRK 1/2/3 genes.

As part of the initial assessment of patients with metastatic pancreatic cancer, the updated guideline recommends early testing for actionable genomic alterations, because the results of testing can lead to therapies and clinical trials of targeted therapies. Early testing is recommended to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy.

Any decision to test for actionable genomic alterations should involve a discussion between the patient and physician regarding the frequency of actionable findings, the treatment implications of testing results, and genetic counseling related to germline testing.

Treatment with larotrectinib or entrectinib is now recommended for patients with tumors harboring NTRK fusions, according to the document, published in the Journal of Clinical Oncology.

For patients who have a germline BRCA1 or BRCA2 mutation and who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks, options for continued treatment include chemotherapy or treatment with the PARP inhibitor olaparib.

As with the earlier guidelines, there continue to be no data on the duration of cancer-directed therapy. Accordingly, the panel recommends that “an ongoing discussion of the goals of care and assessment of treatment response and tolerability should guide decisions to continue or to hold or terminate cancer-directed therapy.”

The guideline concludes, “ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care, and that all patients should have the opportunity to participate.”

Dr. Margaret A. Tempero, director of the UCSF Pancreas Center at the University of California, San Francisco, told Reuters Health by email, “The molecular profiling on tumor tissue and the germline testing (deserve emphasis). You can’t get to the choice of drugs unless you do this first.”

“These changes affect less than 10% of patients,” added Dr. Tempero, who was not involved in the guideline development. “Finding new transformative and effective therapies for the majority remains a high priority.”