FLASCO Faculty Flesh Out Case Studies in GI Cancers

We recently traveled to Miami, Florida, for a State of the Science Summit™ on Gastrointestinal Malignancies. Targeted therapy has become an important fixture in oncogene-driven cancers, particularly in BRAF V600E-mutant metastatic colorectal cancer (mCRC) and BRCA-mutant metastatic pancreatic cancer. Although the jury is still out on the actionability of a HER2 mutation versus HER2 overexpression or amplification in colorectal cancer, the importance of performing next-generation sequencing has become apparent with all of the data reported from pivotal phase III studies, such as BEACON CRC and POLO.

Historically, patients with BRAF V600E-mutant mCRC have had poor prognosis. However, data from the BEACON CRC trial showed favorable progression-free survival (PFS) and overall survival with the combination of encorafenib, cetuximab with or without binimetinib compared with investigator’s choice of either cetuximab and irinotecan or cetuximab and FOLFIRI in patients who progressed on 1 or 2 lines of therapy. In August 2018, the FDA granted a breakthrough therapy designation to the triplet for use in patients with BRAF V600E-mutant mCRC who received 1 or 2 lines of therapy. In December 2019, the FDA granted a priority review designation to a supplemental new drug application for the combination of encorafenib and cetuximab in the same indication.

In pancreatic cancer, data from the phase III POLO trial showed a PFS advantage with olaparib compared with placebo in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease had not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. In December 2019, the FDA approved the PARP inhibitor and the BRACAnalysis CDx^® companion diagnostic to determine which patients are eligible to receive the therapy. The approval was announced after a positive recommendation from the agency’s Oncologic Drugs Advisory Committee, which had voted 7 to 5 in favor of the approval.

This week, we sat down with Atif Hussein, MD, of Memorial Cancer Institute, and A. Craig Lockhart, MD, MHS, of Sylvester Comprehensive Cancer Center, to discuss the role of targeted therapy in colorectal and pancreatic cancer, the utility of regorafenib (Stivarga) and TAS-102 (trifluridine/tipiracil; Lonsurf) alone and in combination, and the importance of conducting next-generation sequencing. Dr. Hussein is chief of Oncology and Hematology Services at Memorial Cancer Institute and Dr. Lockhart is a professor and associate director for Regional and Strategic Clinical Research Affiliations at Sylvester Comprehensive Cancer Center.

First, we hear from Dr. Hussein, who presents a case of a 38-year-old woman who presented with progressive abdominal pain, progressive constipation, and weight loss in 2018. Listen on to hear the complete case presentation and potential course of treatment.

Next, Dr. Hussein presents a case of a 66-year-old man who was diagnosed with stage II transverse colorectal cancer who underwent colonic resection. No adjuvant therapy was given. Eighteen months later, his CEA was found to be elevated and imaging studies revealed multiple bilobar hepatic lesions. Listen on to hear the full case presentation and treatment possibilities for this patient.

Next, Dr. Hussein, shares a case of a 49-year-old man who presented with progressive abdominal right upper quadrant pain. He was found to have obstructive jaundice with bilirubin of 9 mg/dL. Imaging studies revealed a fullness, but no discrete masses, in the head of the pancreas. Endoscopic ultrasound revealed a mass in the pancreatic head with one 8 millimeter node. Listen on to hear the complete case presentation and recommended course of therapy.

Finally, Drs. Lockhart and Hussein reflect on noteworthy studies from the 2020 Gastrointestinal Cancers Symposium.

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