D0137 - Microscopic Colitis Induced by KRAS Targeted Therapy, Sotorasib

Islam Younes, MBBCh¹, Giorgi Khardziani, MD², Walaa Hammad, MBBCh³, Amr Saber, MBBCh⁴, Ahmed Omran, MBBCh¹, Daniel Bodek, DO^1
1Rutgers Health/Trinitas Regional Medical Center, Elizabeth, NJ; ²Overlook Medical Center / Atlantic Healthcare, Summit, NJ; ³AIN Shams University Hospital, Abbasia, Al Qahirah, Egypt; ⁴siParadigm Diagnostic Informatics, Pine Brook, NJ

Introduction: Microscopic colitis is a chronic inflammatory condition in the colon where the patients usually present with chronic non-bloody, watery diarrhea. Colonoscopy usually shows normal mucosa and the diagnosis is established by colon biopsies that show the characteristic submucosal histologic changes. Microscopic colitis has been associated with smoking and different medications such as NSAIDs, PPIs, and SSRIs. We present a case of microscopic colitis that was found to be associated with the KRAS inhibitor, Sotorasib.

Case Description/Methods: A 52-year-old non-smoker male with a history of stage IV poorly differentiated lung adenocarcinoma status post radiation and chemotherapy 6 months ago, clostridium difficile diarrhea six months ago, and pulmonary embolism on Rivaroxaban. The patient was then started on KRAS targeted therapy with Sotorasrib 960 mg daily given the progression of his carcinoma. One month later, he developed watery diarrhea. PCR stool, including clostridium difficile, was unremarkable. Sotorasib dose was decreased to 480 mg daily and then to 240 mg daily, however; he continued to have severe diarrhea and then was admitted to the hospital. He stated that he had been having 6-8 episodes of loose watery non-bloody stools associated with poor appetite and decreased oral intake. He denied any nausea or vomiting. The patient was started on IV fluids and Imodium while Sotorasib was held. CT abdomen with oral and IV contrast showed stable metastatic right iliopsoas mass and mild colonic wall thickening. Colonoscopy was done and showed grossly normal colonic and rectal mucosa. The cecum, ascending, and sigmoid colon biopsies showed inflammatory granulation tissues consistent with microscopic colitis. Diarrhea significantly improved after discontinuation of Sotorasib. The patient was discharged once his diarrhea resolved which did not recur afterward.

Discussion: Sotorasib is an antineoplastic, KRAS inhibitor, which is typically used in advanced non-small-cell lung cancer. Diarrhea has been established as a common side effect (47 %) of this medication that can limit its use in the indicated cases. This is the first case report in the literature, up to our knowledge, that shows an association between microscopic colitis and Sotorasib. Understanding the underlying pathophysiology of diarrhea as a limiting side effect of Sotorasib may help the patients to tolerate such medication.


Disclosures:


Islam Younes, MBBCh¹, Giorgi Khardziani, MD², Walaa Hammad, MBBCh³, Amr Saber, MBBCh⁴, Ahmed Omran, MBBCh¹, Daniel Bodek, DO¹. D0137 - Microscopic Colitis Induced by KRAS Targeted Therapy, Sotorasib, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.