Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer

Abstract

IMPORTANCEThe prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. DESIGN, SETTING, AND PATIENTS CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. INTERVENTIONS After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m 2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.RESULTS A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). CONCLUSIONS AND RELEVANCEAmong patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.

Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma

“…Adjuvant chemotherapy is considered the standard of care for patients with resectable pancreatic ductal adenocarcinoma. 6,7 Pyrimidine analogs (gemcitabine or 5-fluorouracil (5-FU)) are the most commonly used agents, with gemcitabine demonstrating an improved survival compared with no treatment in CONKO-001, 7 and an improved toxicity profile compared with 5-FU in ESPAC-3. 8 Molecular studies have shown that pancreatic ductal adenocarcinomas contain a high number of gene deletions, mutations, amplifications and rearrangements, 9,10 yet the contribution of these genetic abnormalities to tumor behavior and response to systemic therapy is not well understood.…”

Resektion beim fortgeschrittenen Pankreaskarzinom nach multimodaler Vorbehandlung

“…Die Prognose des Pankreaskarzinoms ist mit einer 5-Jahres-Überlebensrate von weniger als 5 % weiterhin unverändert schlecht. Nur 10-20 % der Patienten präsentieren sich mit lokal resektablen Tumoren bei Diagnosestellung und bei diesen Patienten führt eine Resektion gefolgt von adjuvanter Chemotherapie zu robusten 20 % 5-Jahres-Überlebensraten [23,25], in selektierten Patientengruppen auch 40 % bis hin zu über 50 % [2,11].…”

Are Quality Indicators associated with Postoperative Outcomes after Resection for Pancreatic Adenocarcinoma?

“…Except for surgery, other treatments have shown modest impact on patients' survival and are often underutilized [3][4][5][6][7][8][9]. Since there are no cost-effective screening tests, a high clinical suspicion is necessary for the diagnosis of early stage tumors2 and the majority of patients are diagnosed with locally advanced or metastatic disease [2,3].…”

“…Recent studies have shown that survival of patients with PC has remained rather unchanged over the last decades with only 5-10% being alive after five years [4,10,11]. Besides established prognostic factors such as cellular differentiation, lymph vascular infiltration and tumor stage, there may be other reasons responsible for the low survival rate of these patients.…”

“…Besides established prognostic factors such as cellular differentiation, lymph vascular infiltration and tumor stage, there may be other reasons responsible for the low survival rate of these patients. Several groups have reported that PC patients receive one of the lowest rates of cancer-directed therapy among all the solid tumors [4][5][6][7][8][9][10] and treatments may differ based upon patients' socioeconomic status (education level, income), place of residence (rural vs. urban), number of procedures performed in a health system (low vs. high volume hospital) and physician expertise [4][5][6][7][8][9][10].…”