Dr Park on the Initial Efficacy of Epacadostat Plus Preoperative Chemoradiation in Rectal Cancer

Haeseong Park, MD, MPH, medical oncologist, Gastrointestinal Cancer Treatment Center, Dana-Farber Cancer Center, discusses early efficacy and safety results from a phase 1 translational trial (NCT03516708) investigating treatment with epacadostat plus preoperative chemoradiation in locally advanced rectal cancer.

The phase 1 trial evaluated the safety of IDO1 inhibition with epacadostat alongside neoadjuvant short-course radiation and chemotherapy with capecitabine and oxaliplatin (CAPOX) in locally advanced rectal cancer, Park begins. The study's primary objective was to determine the recommended phase 2 dose (RP2D) of the epacadostat combination, with secondary objectives including assessment of antitumor activity as measured by neoadjuvant rectal (NAR) score, and pathological or clinical complete responses, she adds.

Patients enrolled onto the study and received either 300 mg, 400 mg or 600 mg twice-a-day of epacadostat alongside 5Gy x 5 fractions of radiation, Park elucidates. This was followed by 6 cycles of CAPOX for approximately 24 weeks until the day of surgery, she reports.Patients in the control arm received the same treatment without epacadostat.

Findings from the study were presented at the 2024 AACR Annual Meeting and showed that the efficacy of the epacadostat combination was comparable to standard short-course radiation therapy alone in patients with rectal cancer. Furthermore, assessment of antitumor activity demonstrated lower NAR scores post-treatment, which indicates a more favorable tumor response vs standard therapy, Park shares. Despite the study's small cohort, these results suggest the efficacy of this combined regimen, she adds.

The most common adverse effect (AE) observed in patients treated with the epacadostat combination was diarrhea, which is typical of radiation and chemotherapy treatments, she continues. Notably, more than half of the patients in the study presented with advanced disease stages, including T4 and N2 diseases, underscoring the challenging nature of the cases evaluated. Researchers are actively investigating whether the combined treatment approach contributed to these outcomes, Park elucidates

Two patients experienced dose-limiting toxicities at the 600 mg dose, including elevated alanine aminotransferase and aspartate aminotransferase levels attributed to epacadostat, and a grade 3 rash. Although most cases of rash were manageable, investigators determined that 400 mg was the RP2D for further investigation, Park concludes.