Practice-changing research in GI cancer

Daniel G. Haller, MD, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to review the top three GI cancer trials presented at the 2019 ESMO World Congress on Gastrointestinal Cancer, and how they are changing practice.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the difficulty in using age to guide cancer treatment.

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BEACON trial for colorectal cancer

• Patients with BRAF mutations have a poor prognosis and typically fail treatment prior to second line therapy.
• BEACON is a phase 3 trial that was designed to test BRAF/MEK combination targeted therapies in patients with BRAF-mutated metastatic colorectal cancer.
• The study found that the three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival in patients with BRAF-mutated metastatic colorectal cancer. The response rate for targeted triple therapy was 26%, compared with 2% for controls.
• It may be important for all patients with colorectal cancer to be tested for BRAF.

IDEA trial in colon cancer

• Use of oxaliplatin in chemotherapy treatment regimens results in improvement in outcomes for patents with stage III colon cancer. However, treatment with oxaliplatin can cause disabling neuropathy, which is directly proportional to the cumulative dose administered.
• The IDEA (International Duration Evaluation of Adjuvant Therapy) trial combines data from six trials, in which patients with stage III colon cancer were randomized to receive 3 months or 6 months of adjuvant chemotherapy with a fluoropyrimidine plus oxaliplatin.
• The incidence of peripheral neuropathy was significantly reduced with the 3-month regimen, as compared with 6- month treatment. Survival data for 3 months of treatment with oxaliplatin are still pending.
• In patients with positive circulating tumor DNA (ctDNA) prior to adjuvant therapy, 6 months of treatment was preferable.

Pembrolizumab, plus or minus chemotherapy, in gastric cancer

• This was a well-balanced three-arm study which included groups of patients treated upfront with pembrolizumab alone, chemotherapy alone, or a combination of pembrolizumab with chemotherapy. The primary endpoint was overall survival.
• Pembrolizumab was noninferior to chemotherapy if the combined positive score (CPS) was greater than 1. Pembrolizumab plus chemotherapy was not superior, even for CPS greater than 0.85.
• When pembrolizumab is started alone, patients drop off quickly. However, the responders to pembrolizumab have a long duration of response. It may be beneficial to start with chemotherapy and switch to targeted therapy when the side effects of chemotherapy become too great.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz