Addition of stereotactic body radiotherapy (SBRT) to systemic chemotherapy in locally advanced cholangiocarcinoma (CC) (ABC-07): Results from a randomized phase II trial.
Authors: Maria A. Hawkins, Juan W. Valle, Harpreet Singh Wasan, Mark Harrison, Helen Morement, Prakash Manoharan, Ganesh Radhakrishna, David Eaton, Douglas Brand, Temi Adedoyin, Ka Man Mak, Natasha Hava, Shumona Shelly, Memuna Rashid, Andre Lopes, John A Bridgewater
Journal: Journal of Clinical Oncology (2024)

4006 Background: Locoregional treatments for inoperable, non-metastatic CC remain undefined. Single arm phase 2 data suggested that SBRT may improve clinical outcomes. We aimed to investigate the efficacy and safety of the addition SBRT with CisGem in locally advanced inoperable CC. Methods: ABC-07 (ISRCTN:10639376) is a phase II multicentre randomized trial for patients with inoperable, histologically confirmed locally advanced CC, WHO performance status 0-1. After registration patients showing no progression after 4 cycles of CisGem were randomized (2:1) for treatment after completing six cycles: either SBRT (50 Gy in 5 fractions or 67.5 Gy in 15 fractions, based on tumour size) or two additional cycles (cycles 7 and 8) of CisGem (CG-only). Primary endpoint was progression free survival (PFS). With 80% power and a 15% one-sided alpha, the study planned to randomize 65 patients to detect a median PFS increase from 10.4 to 17.4 months. Secondary endpoints included overall survival (OS), toxicity and patterns of failure. RT quality assurance was undertaken. Results: Between March 2016 and August 2022, 16 UK centres randomized 69 patients (SBRT, 45; CG only, 24). Median age was 66 (38 to 83) yrs, 58 (84.1%) perihilar location, 48(69.6%) stent in situ, median tumor size was 3.5cm (range 0.6-10.5). The median follow-up time was 20.7 months. In the SBRT arm, 43 completed 6 cycles CisGem (96%) and 41 (91%) received SBRT. In the CG-only arm, 18 (75%) completed 8 cycles. The median PFS from randomization was 8.6 and 9.0 months in the SBRT and CG-only arms, respectively (HR: 1.00; 95% CI: 0.58,1.70; p = 0.989). The first PFS events were 7 (16%) local and 24 (53%) metastatic relapses for SBRT, versus 7 (29%) and 7 (29%) in the CG-only arm, respectively. From registration, median OS time was 23.4 (95% CI: 14.6, 27.7) months for SBRT and 17.2 (95% CI: 10.2, NR) months for CG-only arm. Post-randomization, OS was 19.4 months (11.2, 24.6) for SBRT and 14.2 (7.0, NR) months for CG-only (HR: 0.79; 95% CI: 0.41,1.51; p = 0.47). Adverse events of grade ≥3 were observed in 33 (73%) and 21 (88%) patients in SBRT and CG-only arms, respectively. Of the infections, of which biliary sepsis was common, pre-cycle 6, SBRT had 19 (42%) cases vs. 7 (29%) in CG-only; post-cycle 6, SBRT had 17 (38%) sepsis cases vs. 6 (25%) in CG-only. There was 1 Grade 3 duodenal hemorrhage and 1 death due to sepsis in the SBRT arm. Primary causes of death included disease (20, 44% vs 11, 46%), sepsis (5, 11% vs 3, 13%), and hepatic failure (0 vs 3, 13%) for the SBRT and CG-only arms, respectively. Conclusions: SBRT did not show a PFS advantage over CG-only, yet a longer median OS time and better primary tumour control were observed without safety concerns. However, more mature survival data is still needed. Clinical trial information: 10639376.