CHICAGO — A chemotherapy regimen composed of epirubicin, cisplatin and capecitabine demonstrated higher overall toxicity without improving OS compared with cisplatin and 5 fluorouracil in patients with surgically treated esophageal cancer, according to the results of a phase 3 trial presented at the ASCO Annual Meeting.
However, the treatment regimen resulted in some benefit in PFS, DFS and tumor regression at resection, results showed.
A neoadjuvant chemotherapy regimen composed of two cycles of cisplatin and 5 fluorouracil followed by surgery serves as the standard of care for locally advanced esophageal cancer, according to study background.
“In the OEO2 trial [Allum WH, et al. J Clin Oncol. 2009;doi:10.1200/JCO.2009.22.2083], two cycles of cisplatin and 5 fluorouracil increased 2-year survival rates from 34% to 43%,” David Cunningham, MD, FRCP, head of the gastrointestinal unit at The Royal Marsden Hospital in Surrey, U.K., said during a presentation. “The MAGIC trial [Cunningham D, et al. N Engl J Med. 2006:doi:10.1056/NEJMoa055531.] showed that epirubicin, cisplatin and capecitabine improved survival from 23% to 36%. This particular study was designed to increase the intensity and number of cycles of chemotherapy prior to surgery.”
Cunningham and colleagues evaluated data from 897 patients (median age, 62 years; interquartile range [IQR], 56-67; 90% male) with lower esophageal and junctional adenocarcinoma. The researchers randomly assigned patients to receive the standard chemotherapy regimen (n = 451) or four cycles of epirubicin, cisplatin and capecitabine (ECX; n = 446) followed by esophagectomy with 2-field lymphadenectomy.
OS served as the primary endpoint. PFS, DFS, pathological R0 resection rate, Mandard grade and quality of life served as secondary endpoints.
Ninety-six percent of patients assigned cisplatin and 5 fluorouracil received two treatment cycles and 89% of patients assigned ECX received more than three cycles.
Overall, 315 deaths occurred among patients who received the standard chemotherapy regimen and 298 deaths occurred among patients assigned ECX. The trial combination did not exhibit statistically significant superiority to the standard chemotherapy regimen (HR = 0.92; 95% CI, 0.79-1.08).
Similar 3-year survival rates occurred among patients assigned the trial combination and the standard chemotherapy regimen (42% vs. 39%).
Comparable rates of post-operative complications occurred on the standard chemotherapy and ECX arms (57% vs. 62%). Researchers also observed similarly low rates of death at 30 days (2% for both) and 90 days (4% vs. 5%) following surgery.
However, researchers observed slightly improved PFS (HR = 0.86; 95% CI, 0.74-1.01) and DFS (HR = 0.88; 95% CI, 0.75-1.03) among patients who received ECX.
“At the present time, 115 patient who received [the standard chemotherapy regimen] and 136 patients who received ECX are currently alive and progression-free,” Cunningham said.
“Although not statistically significant, clearly the HR is in favor [of ECX].”
More patients assigned ECX than standard chemotherapy achieved R0 resection rates (66% vs. 60%), a Mandard grade of 3 or lower (32% vs. 15%) and complete response (11% vs. 3%).
Younger patients (aged ≤ 70 years) and patients with node-negative disease exhibited greater benefit from ECX compared with the standard chemotherapy regimen, Cunningham said.
Researchers observed a significantly lower incidence of grade 3 or 4 adverse events among patients who received the standard chemotherapy regimen (30% vs. 47%; P < .001).
“The survival in both arms of this trial were better than expected,” Cunningham said. “This is encouraging for patients with esophageal gastric cancer. We are also seeing a trend towards improvement with ECX with regard to tumor regression rates — which were significantly better — and a PFS that was not quite significantly better. This did not, however, translate into a survival advantage.” – by Cameron Kelsall
Alderson D, et al. Abstract 4002. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: Cunningham reports receiving research funding from Amgen, AstraZeneca, Celgene, MedImmune, Merck Serono, Merrimack and Sanofi. Please see the abstract for a list of all other researchers’ relevant financial disclosures.