Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX).

person Erqi L. Pollom Stanford Hospital and Clinics, Palo Alto, CA info_outline Erqi L. Pollom, George A. Fisher, Andrew Shelton, Tyler Paul Johnson, Christopher Chen, Scott Jackson, Shagufta Shaheen, Thomas Holden, Jeffrey Bien, Daniel King, Arden M. Morris, Cindy Kin, Aaron Dawes, Natalie Kirilcuk, John Gahagan, Lucas Vitzthum, Vipul Sheth, Eleanor Brown, Aniket Pratapneni, Daniel Tandel Chang

Authors person Erqi L. Pollom Stanford Hospital and Clinics, Palo Alto, CA info_outline Erqi L. Pollom, George A. Fisher, Andrew Shelton, Tyler Paul Johnson, Christopher Chen, Scott Jackson, Shagufta Shaheen, Thomas Holden, Jeffrey Bien, Daniel King, Arden M. Morris, Cindy Kin, Aaron Dawes, Natalie Kirilcuk, John Gahagan, Lucas Vitzthum, Vipul Sheth, Eleanor Brown, Aniket Pratapneni, Daniel Tandel Chang Organizations Stanford Hospital and Clinics, Palo Alto, CA, Department of Medicine, Stanford University School of Medicine, Stanford, CA, Stanford University Medical Center, Stanford, CA, Stanford University Hospital and Clinics, Palo Alto, CA, Stanford University School of Medicine, Palo Alto, CA, Stanford, Palo Alto, CA, Stanford University Medical Center, Palo Alto, CA, Stanford University, Palo Alto, CA, Stanford University School of Medicine, Stanford, CA, Stanford University, Palo Alto, Stanford University, Stanford, CA Abstract Disclosures Research Funding No funding sources reported Background: Patients (pts) with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy may be safely observed and spared the long-term sequela of total mesorectal excision (TME). We hypothesized that a novel neoadjuvant regimen (short-course radiation with boost and FOLFOXIRI chemotherapy) would achieve higher cCR rates than historical controls. Methods: We conducted a single-arm, phase II study of short-course radiation followed by FOLFOXIRI for pts with >T2N0 or low T2N0M0 rectal adenocarcinoma (NCT04380337). Pts underwent radiation (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by 8 cycles of FOLFOXIRI. Pts were assessed for primary endpoint (cCR) at 8 weeks following chemotherapy. Those who achieved a cCR or near cCR were surveilled. cCR required no tumor on MRI, endoscopy, and if applicable, digital rectal exam. A Simon 2-stage design addressed our primary objective, with interim analyses for futility and toxicity. Assuming a one-sided type 1 error of 0.1, power of 0.9, a null cCR of 0.2 versus an alternate cCR of 0.4, our sample size was 37 pts. Results: Between May 2020 and April 2023, 37 pts enrolled (Table). 25 pts (67.5%) had at least one high risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin [CRM], positive lateral node). All pts completed radiation; 32 pts (86.5%) completed all 8 cycles of chemotherapy. Criteria for futility and safety were met at interim analysis. At primary outcome assessment, 9 (24.3%) pts achieved a cCR and 8 (21.6%) pts achieved a near cCR. 3 pts who initially had a cCR developed local regrowth and underwent TME. Of the pts who had a near cCR, 5 developed local regrowth and underwent TME while 3 pts achieved delayed cCR. Serious adverse events occurred in 5 (13.5%) pts; 1 patient had non-hematologic grade 4 toxicity at least possibly related to treatment. There were no treatment-related deaths. The12-month TME-free survival for all patients was 37.2%, and for patients with T3 and T4 tumors was 44.3% and 12.5%, respectively. Conclusions: Short-course radiation followed by FOLFOXIRI was feasible and safe. In this high-risk cohort of pts with rectal cancer, 24.3% of pts had a cCR at time of primary assessment. Clinical trial information: NCT04380337. Baseline characteristics of enrolled pts. Baseline characteristics. Gender Female 13 (35.1%) Male 24 (64.9%) Age, years Median [IQR] 52 [44, 61] Race White 26 (70.3%) Asian 10 (27.0%) Native-Hawaiian or Other Pacific Islander 1 (2.7%) ECOG 0 26 (70.3%) 1 11 (29.7%) Clinical T Stage cT2 3 (8.1%) cT3 26 (70.3%) cT4 8 (21.6%) Clinical N Stage cN0 7 (18.9%) cN1 15 (40.5%) cN2 15 (40.5%) Distance from anal verge, cm Median [IQR] 7.00 [3.30, 8.80] EMVI Absent 24 (64.9%) Equivocal 5 (13.5%) Present 8 (21.6%) Lateral lymph node involvement Absent 32 (86.5%) Present 5 (13.5%) Threatened CRM No 18 (52.9%) Yes 16 (47.1%)

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