Abstract 1470P
Background
Of the only 20% of patients (pts) with resectable pancreatic ductal adenocarcinoma (PDA), overall survival (OS) remains low as cancer recurs in 80% of cases within 2 years of surgery. Epigenetic modulators such as 5-azacitidine (CC-486) may reactivate tumor suppressor genes, delay recurrence, and sensitize PDA to future chemotherapy.
Methods
This was a phase II study of CC-486 vs. observation (OBS) in rPDA pts harboring high-risk features (stage pN1-2, R1 margins, or elevated CA 19-9 level) with no evidence of disease following standard adjuvant therapy. Pts were randomized to oral CC-486 treatment (300mg daily on days 1-21 on a 28-day cycle) or OBS for up to 12 cycles or until disease relapse/unacceptable toxicities. Following recurrence, records of next-line therapies, imaging, & survival were obtained. The primary endpoint was progression-free survival (PFS) - time from randomization to recurrence (imaging/biopsy confirmed or death). Secondary endpoints included OS & 1st-line metastatic therapy outcomes (PFS & overall response [ORR]).
Results
Forty-eight pts (24 in CC-486 arm, 24 in OBS arm) were randomized: median age 65 (range 36-81), 52% male, 73% node positive, 50% elevated CA 19-9, 21% R1 resection, 65% and 100% received perioperative cRT and chemotherapy, respectively. Median time from surgery to randomization was 10 months (mo) (range 2.9-36.8). For the CC-486 arm, median treatment duration was 5.5 mo (range 1.3 to 12.8) with 14 treatment-related grade 3 or 4 AEs among 6 pts (23%) resulting in dose-reduction & delay. Four pts (17%) discontinued therapy due to AE. One participant progressed at the time of randomization and was excluded from the PFS analysis. With median follow-up of 20.5 mo (range 0.03-79.7), 38 pts recurred (72% radiographic, 9% clinical). Median PFS in confirmed cases was 7.8 and 8.9 mo (HR 1.01, 95% CI 0.40-2.03) for CC-486 and OBS, respectively. Median OS (2-yr OS%) was 21.9 (46%) and 25.6 mo (61%) in CC-486 and OBS, respectively. (HR 1.01, 95% CI 0.54-2.26). Response to chemotherapy in the metastatic setting in the CC-486 vs OBS arms will be reported at the meeting.
Conclusions
Treatment with CC-486 following adjuvant therapy did not prolong time to relapse in patients with high-risk rPDA nor improve overall survival.
Clinical trial identification
NCT01845805.
Editorial acknowledgement
Legal entity responsible for the study
Johns Hopkins University.
Funding
Gateway Foundation, Celgene (BMS).
Disclosure
All authors have declared no conflicts of interest.