medwireNews: Adding capecitabine to gemcitabine in the adjuvant setting significantly improves overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma, the ESPAC-4 trial shows.
Median OS was 28.0 months for participants who received gemcitabine plus capecitabine after undergoing complete macroscopic resection and 25.5 months for their counterparts given gemcitabine alone, equating to a significant hazard ratio (HR) for death of 0.82.
The 5-year OS rates were estimated at 28.8% and 16.3%, respectively.
These results indicate that the combination should be the “new standard of care” for this patient population, the investigators say in The Lancet, a view also endorsed by Gaël Deplanque (Hôpital Riviera-Chablais, Vevey, Switzerland) and Nicolas Demartines (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) in an accompanying commentary.
The commentators highlight that “even if modest, these figures are encouraging in a disease with such high mortality.”
In the phase III trial, 364 patients were randomly assigned to receive six cycles of gemcitabine 1000 mg/m2 weekly plus oral capecitabine 1660 mg/m2 daily, each on a 3-weeks on, 1-week off schedule, whereas 366 participants received gemcitabine alone.
The combination improved survival in “most clinical subgroups,” the researchers note, including patients who had positive (R1) resection margins, although the degree of benefit was not as great as for those with negative (R0) margins, with corresponding HRs of 0.90 and 0.68.
During a median follow-up of 43.2 months, adverse events of grade 3 or 4 occurred in 62.9% of participants given the combination and 53.5% of those treated with gemcitabine alone. Neutropenia, hand–foot syndrome, and anemia occurred significantly more often in the combination arm, while infective manifestations were more common in the monotherapy arm.
John Neoptolemos, from the University of Liverpool in the UK, and fellow investigators say that the toxicity was “acceptable” and “manageable with protocol driven capecitabine dose reduction when required.”
Furthermore, the adverse events appeared not to affect quality of life, with no significant between-group differences noted at 3, 6, or 12 months.
To further improve these results, Deplanque and Demartines say that identifying a biomarker “that could guide the choice of treatment or even surgery” is crucial.
“The results of several other large adjuvant trials with new drugs or a combination of drugs are also eagerly awaited and it is likely that more chemotherapy will translate into more patients being cured.
“But again, this will be only for a small subset of patients with pancreatic cancer who received surgery,” say the commentators, adding: “More surgery is therefore clearly needed if we want to cure more patients, but more surgery means the possibility to offer surgery earlier in the disease evolution, and as a consequence more often.”
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