Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation

• Published in: International journal of radiation oncology, biology, physics Vol. 114; no. 3; pp. 444 - 453
• Main Authors: Koay, Eugene J., Zaid, Mohamed, Aliru, Maureen, Bagereka, Polycarpe, Van Wieren, Arie, Rodriguez, Maria Jovie, Jacobson, Galia, Wolff, Robert A., Overman, Michael, Varadhachary, Gauri, Pant, Shubham, Wang, Huamin, Tzeng, Ching-Wei, Ikoma, Naruhiko, Kim, Michael, Lee, Jeffrey E., Katz, Matthew HG, Tamm, Eric, Bhosale, Priya, Taniguchi, Cullen M., Holliday, Emma B., Smith, Grace L., Ludmir, Ethan B., Minsky, Bruce D., Crane, Christopher H., Koong, Albert C., Das, Prajnan, Wang, Xuemei, Javle, Milind, Krishnan, Sunil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022
• Subjects: Albumins; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomarkers; Capecitabine; Carcinoma, Pancreatic Ductal - diagnostic imaging; Carcinoma, Pancreatic Ductal - therapy; Deoxycytidine - therapeutic use; Humans; Induction Chemotherapy - methods; Paclitaxel; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - therapy
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2022.06.089

Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.