353 - Safety and Efficacy Results of a Phase II Clinical Trial Evaluating Moderately-Hypofractionated Chemoradiotherapy for Pancreatic Ductal Adenocarcinoma

K. W. Merrell¹, C. L. Hallemeier¹, W. S. Harmsen², J. B. Ashman³, M. Truty⁴, J. L. Leenstra¹, M. A. Timm⁵, D. Owen¹, C. Thiels⁴, C. C. H. Stucky⁶, M. Neben Wittich¹, T. Bekaii-Saab⁶, W. G. Rule³, Y. Garces¹, R. R. McWilliams⁵, S. C. Lester¹, M. G. Haddock¹, T. T. W. Sio³, and K. R. Jethwa¹; ¹Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ²Department of Biostatistics and Health Sciences Research, Mayo Clinic, Rochester, MN, ³Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, ⁴Department of Surgery, Mayo Clinic, Rochester, MN, ⁵Mayo Clinic, Rochester, MN, ⁶Mayo Clinic, Phoenix, AZ

Purpose/Objective(s): Chemoradiotherapy (CRT) is a standard treatment for pancreatic cancer, though there is no universal consensus on RT dose. Prospective data on hypofractionated CRT regimens are limited. The purpose of this clinical trial is to evaluate the safety and efficacy of moderately-hypofractionated CRT. Materials/

Methods: This is a single arm, prospective phase II clinical trial conducted at a multi-site, high-volume institution. Patients with non-metastatic pancreatic cancer who were suitable for curative intent CRT after induction chemotherapy were eligible. Patients received 45Gy to gross disease and 37.5Gy to an elective nodal expansion delivered over 15 daily fractions with concurrent capecitabine. The primary endpoint was the rate of acute grade 3+ adverse events (AE) at least possibly related to CRT. Acute AE was defined as AE occurring during or within 3 months of CRT completion or up to the surgical date for those who underwent resection. Secondary endpoints include progression-free survival (PFS), overall survival (OS), distant metastasis (DM) and patient reported outcomes using the Functional Assessment of Cancer Therapy Hepatobiliary (FACT-Hep) questionnaire. The study was powered to detect non-inferior acute grade 3+ AE relative to a historical control rate of 15% identified in the LAP07 trial.
Results: Between 2/2019 and 8/2021, 103 patients were enrolled with 98 evaluable. The median follow up was 3.2 years (95% CI: 2.9-4.0) for living patients. The median age was 66 years (range, 38-85) and 59% were male. NCCN resectability status criteria was 9%, 43% and 48% for resectable, borderline resectable, and locally advanced, respectively. Median baseline and pre-CRT CA 19-9 were 65.5 U/mL (IQR: 17-283) and 25.0 U/mL (IQR: 9-64), respectively. Patients received a median of 8 cycles (IQR: 5-10) of chemotherapy, most commonly mFOLFIRINOX (90%), prior to CRT. A total of 71 patients underwent resection with a 97% R0 rate. CAP treatment response score of 0 or 1 was 28%. The primary endpoint was met and acute grade 3+ AE at least possibly related to CRT was 2.4% (95% CI: 0.3-8.3). Mean FACT-Hep scores decreased from 116 to 71 immediately after CRT but returned to 116 when measured 12-months after CRT. The DM rate at 2 years was 20% (95% CI: 13-32) and 28% (95% CI: 15-53) for patient who underwent resection vs. CRT alone, respectively. The 2-year PFS and OS for patients who underwent resection was 48.5% (95% CI: 38-62) and 64.4% (95% CI: 54-77%), respectively. The 2-year PFS and OS for CRT alone patients was 12% (95% CI: 4-35) and 20% (95% CI: 9-44%), respectively. On multivariable analysis, surgery was associated with reduction in DM (P=0.04; HR=0.37; 95% CI: 0.1-0.9), PFS (P=<0.001; HR=0.35; 95% CI: 0.2-0.6), and OS (P= 0.001; HR=0.36; 95% CI: 0.2-0.7).
Conclusion: In this prospective phase II trial, the primary endpoint was met, suggesting moderately-hypofractionated CRT is safe and effective relative to historical conventionally fractionated CRT controls.