Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer

Abstract

Background: SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes.

Methods: Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m^-2 days 1, 8, 15; CAP 830 mg m^-2 days 1-21 q28 days) patients with stable/responding disease, tumour ⩽6 cm, and WHO Performance Status 0-1 were randomised to receive one cycle GEMCAP followed by CAP (830 mg m^-2 b.d. on weekdays only) or GEM (300 mg m^-2 weekly) with radiation (50.4 Gy per 28 fractions).

Results: One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9-18.7). Updated median OS was 17.6 months (95% CI: 14.6-22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1-16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38-1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0-15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8-12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32-1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l^-1, and shorter tumour diameter predicted improved OS. CAP-CRT, age ⩾65 years, better performance status, CA19.9 <46 IU ml^-1 predicted improved OS and PFS in the pre-radiotherapy model. Nine-month PFS was highly predictive of OS.

Conclusions: CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml^-1 after induction chemotherapy are more likely to benefit from CRT.

Figure 1

CONSORT flow diagram of trial participants.

Figure 2

Kaplan–Meier curves of survival.(A) OS and PFS (all registered patients). Median OS: 12.6 months (95% CI: 11.3–14.9). Median PFS: 9.2 months (95% CI: 7.7–10.3). (B) OS by treatment arm (randomised patients). Median OS: CAP-CRT: 17.6 months (95% CI: 14.6–22.7). GEM-CRT: 14.6 months (95% CI: 11.1–16.0). HR: unadjusted: 0.73 (95% CI: 0.46–1.18, P=0.203). Adjusted: 0.68 (95% CI: 0.38–1.21, P=0.185). (C) PFS by treatment arm (randomised patients). Median PFS: CAP-CRT: 12.0 months (95% CI: 10.0–15.2). GEM-CRT: 10.4 months (95% CI: 8.8–12.7). HR: unadjusted: 0.73 (95% CI: 0.44–1.23, P=0.244). Adjusted: 0.60 (95% CI: 0.32–1.14, P=0.120). (D) LPFS by treatment arm (randomised patients). (E) DPFS by treatment arm (randomised patients).