Definitive chemoradiotherapy affords excellent survival in oesophageal cancer
The conventional cisplatin–capecitabine-based definitive chemoradiotherapy (dCRT) appears to be an effective treatment option in patients with oesophageal cancer, providing excellent survival benefit with a low long-term toxicity, according to a mature analysis of the SCOPE-1 study.
SCOPE-1 was a phase II/III trial that included 258 patients (median age 66.7 years; 56.2 percent male; 60.1 percent had stage III disease; 72.9 percent had squamous cell histology) with nonmetastatic carcinoma of the oesophagus. These patients were randomized to receive four cycles of either dCRT alone (cisplatin 60 mgm−2 on day 1; capecitabine 625 mgm−2 twice daily on days 1 to 21; n=129) or dCRT with cetuximab (400 mgm−2 on day 1 followed by 250 mgm−2 weekly; n=129). Radiotherapy at 50 Gy dose in 25 fractions was concurrently administered during cycles three and four. Results demonstrated that the addition of cetuximab was associated with worse survival outcomes and greater toxicity. [Lancet Oncol 2013;14:627–637]
With the aim of assessing the long-term outcomes in SCOPE-1, the present analysis found that the median overall survival (OS) improved in the dCRT arm (34.5 vs 25.4 months in the initial report). There was no significant between-group difference in OS, which nevertheless remained higher in the dCRT vs cetuximab arm (24.7 months with cetuximab; adjusted hazard ratio [aHR], 1.15; 95 percent CI, 0.84 to 1.57; p=0.388). [Br J Cancer 2017;116:709–716]
Factors associated with improved OS included earlier stage, full-dose radiotherapy and higher cisplatin dose intensity.
The progression-free survival (PFS) data further indicated the superiority of dCRT alone to the cetuximab combination (median PFS, 24.1 vs 15.9 months), although the difference did not reach significance (aHR, 1.20; 0.87 to 1.66; p=0.220). Local progression within radiation field was statistically higher in the cetuximab arm (p=0.062).
The survival advantage observed in the dCRT arm was maintained in a sensitivity analysis that included only patients who were alive at treatment conclusion. A total of 84 and 90 patients had died in the dCRT and cetuximab arms, respectively, after a median follow-up of 46.2 months.
Noting the encouraging long-term survival, researchers said: “SCOPE-1 reassures us that dCRT is not an unreasonable alternative to surgery, particularly in patients with borderline fitness where surgery is considered a high-risk procedure. In addition, local recurrence, often raised as an important weakness of dCRT over surgery, was lower in this trial when compared with other historic reports of dCRT.” [J Clin Oncol 2002;20:1167–1174; Clin Oncol (R Coll Radiol) 2003;15:98–108; Ann Oncol 2012;23:1095–1103]
The good survival outcome with dCRT may be attributed to improved patient selection as a result of the introduction of a detailed protocol for staging patients with oesophageal cancer in SCOPE-1 and of a detailed radiotherapy planning guidance document together with a radiotherapy quality assurance (RTQA) programme, they added.
“Given the competing risks of systemic and local failure, efforts should continue to maximise local control through radiotherapy dose intensification (in the context of modern day radiotherapy planning and delivery) and to identify more effective systemic treatments for those patients who do not, or are unlikely to, respond to conventional dCRT,” researchers concluded.