22 (S0266). - Sulindac and Eflornithine Combination Delays the Need for Lower Gastrointestinal Surgery in Familial Adenomatous Polyposis: CPP FAP-310 Trial

Francesc Balaguer, MD¹, Elena Stoffel, MD, MPH², Carol A. Burke, MD, FACG³, Evelien Dekker, MD, PhD⁴, Patrick Lynch, MD, JD⁵, N. Jewel Samadder, MD⁶, Eric Van Cutsem, MD⁷, Paul Wise, MD⁸, Robert Hüneburg, MD⁹, Ramona Lim, MD¹⁰, Michelle Boytim, PhD¹¹, Wei Du, PhD¹², Elizabeth Bruckheimer, PhD¹¹, Alfred Cohen, MD¹¹, James Church, MD³; ¹Hospital Clínic de Barcelona, Barcelona, Catalonia, Spain; ²University of Michigan, Ann Arbor, MI; ³Cleveland Clinic Foundation, Cleveland, OH; ⁴Academic Medical Center, University of Amsterdam, Amsterdam, Noord-Holland, Netherlands; ⁵University of Texas MD Anderson Cancer Center, Houston, TX; ⁶Mayo Clinic, Scottsdale, AZ; ⁷University Hospitals Gasthuisberg / Leuven & KULeuven, Leuven, Brabant Wallon, Belgium; ⁸Washington University School of Medicine, St. Louis, MO; ⁹Universitätsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany; ¹⁰Dana Farber Cancer Institute, Boston, MA; ¹¹Cancer Prevention Pharmaceuticals, Tucson, AZ; ¹²Clinical Statistics Consulting, Blue Bell, PA

Introduction: An international phase III trial (CPP FAP-310) assessed the efficacy of low-dose sulindac, eflornithine, or their combination in reducing the time to disease progression in the lower (LGI) and upper gastrointestinal (UGI) tract in patients with familial adenomatous polyposis (FAP). This post-hoc analysis aimed to evaluate whether this combination of drugs delayed time to clinically significant LGI colorectal polyposis progression and need for FAP-related surgeries compared with monotherapy in FAP patients with an intact colon or with a retained rectum after colectomy with ileorectal anastomosis (IRA) or proctocolectomy with ileal pouch anal anastomosis (IPAA).

Methods: Adults with FAP were randomized 1:1:1 to receive sulindac (150 mg), eflornithine (750 mg), or both once daily for up to 48 months. The LGI study population for this post-hoc analysis was the intent-to-treat population of the trial excluding patients who had undergone prior proctocolectomy with end ileostomy. Efficacy was evaluated as time from randomization to disease progression, defined as need for surgery, and/or excision of >10mm polyps, and/or diagnosis of polyp with high-grade dysplasia.

Results: A total of 158 patients in the CPP FAP-310 trial fit the criteria for this LGI disease progression assessment. FAP disease progression was observed in 2/54 (3.7%), 9/53 (17.0%), and 10/51 (19.6%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions of 80% (hazard ratio [HR]=0.20; 95% CI: 0.05-0.80; p=0.02) and 83% (HR=0.17; 95%CI: 0.04-0.70; p=0.01) between combination and sulindac alone or eflornithine alone, respectively (Figure). The need for surgery as determined by the endoscopist occurred in 0, 7 (13.2%), and 8 (15.7%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions approaching 100% both between the combination and sulindac arms (HR=0.00; 95%CI: 0.00-0.48; p=0.005) and between the combination and eflornithine arms (HR=0.00; 95%CI: 0.00-0.44; p=0.003). Similar reductions were observed in pre-colectomy FAP patients as well as in those with an IRA or an IPAA.

Discussion: Combination therapy with eflornithine and sulindac was superior to either single agent alone in decreasing the risk of colorectal polyposis progression and delaying the need for surgery involving the LGI tract in FAP patients with an intact colon, IRA, or IPAA.


Kaplan-Meier plot on time to disease progression in the LGI population

Disclosures:
Francesc Balaguer: Cancer Prevention Pharmaceuticals – Consultant. Elsevier – Other Financial or Material Support, Editorial fees. FujiFilm – Other Financial or Material Support, Endoscopic equipment on loan. Norgine – Speaker's Bureau. Sysmex – Consultant.
Elena Stoffel indicated no relevant financial relationships.
Carol Burke: Cancer Prevention Pharmaceuticals – Grant/Research Support. Ferring – Grant/Research Support. Freenome – Consultant. Janssen – Grant/Research Support. SLA Pharma – Consultant.
Evelien Dekker: Cancer Prevention Pharmaceuticals – Consultant. FujiFilm – Consultant, Grant/Research Support, Other Financial or Material Support, Endoscopic equipment on loan. GI Supply – Consultant, Speaker's Bureau. Olympus – Consultant, Speaker's Bureau. Roche – Speaker's Bureau. Tillots – Consultant.
Patrick Lynch: Cancer Prevention Pharmaceuticals – Grant/Research Support. SLA Pharma – Consultant.
N. Jewel Samadder: Cancer Prevention Pharmaceuticals – Consultant. Janssen R&D – Consultant.
Eric Van Cutsem: Array – Advisory Committee/Board Member. Bayer – Advisory Committee/Board Member, Grant/Research Support. Biocartis – Advisory Committee/Board Member. Bristol-Myers Squibb – Advisory Committee/Board Member. Celgene – Advisory Committee/Board Member, Grant/Research Support. Daiichi – Advisory Committee/Board Member. GSK – Advisory Committee/Board Member. Halozyme – Advisory Committee/Board Member. Incyte – Advisory Committee/Board Member. Ipsen – Advisory Committee/Board Member, Grant/Research Support. Lilly – Advisory Committee/Board Member, Grant/Research Support. Merck KGaA – Advisory Committee/Board Member, Grant/Research Support. Merck Sharp & Dohme – Advisory Committee/Board Member, Grant/Research Support. Novartis – Advisory Committee/Board Member, Grant/Research Support. Pierre-Fabre – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member, Grant/Research Support. Servier – Advisory Committee/Board Member, Grant/Research Support. Sirtex – Advisory Committee/Board Member. Taiho – Advisory Committee/Board Member.
Paul Wise indicated no relevant financial relationships.
Robert Hüneburg: Cancer Prevention Pharmaceuticals – Consultant.
Ramona Lim indicated no relevant financial relationships.
Michelle Boytim: Cancer Prevention Pharmaceuticals – Employee.
Wei Du: Cancer Prevention Pharmaceuticals – Consultant.
Elizabeth Bruckheimer: Cancer Prevention Pharmaceuticals – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Alfred Cohen: Cancer Prevention Pharmaceuticals – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
James Church indicated no relevant financial relationships.