Geographic variation in systemic treatment of metastatic pancreatic adenocarcinoma (mPAC) patients in real world across Europe
Authors: J. Taieb, A. Carrato, None àMellbring, G. Prager, D. Melisi, B. Westphalen, T. Macarulla Mercadé, N.D´. Esquermes, A. Ferreras, F. De Jong
Journal: Annals of Oncology (2018)

Introduction: mPAC remains associated with poor outcomes. While new compounds/combinations continue to be explored, treatment options are still limited. Data on systemic treatment choices in mPAC and outcomes outside clinical trials are scarce. The goal of this pan-European project was to generate data on diagnosis, treatment patterns and outcomes from the records of patients who completed first-line mPAC treatment across Europe. Methods: In this observational chart review, physicians completed retrospective electronic records from initial diagnosis onwards for patients with the following minimal inclusion criteria: completed first-line mPAC treatment between 07/2014-01/2016 and ≥18 years. In each country, respondents were recruited across different regions and settings (university and general hospitals, cancer and reference centers, office-based specialists) to ensure a balanced selection. Physicians were encouraged to enter as many second-line metastatic patients as possible. We report here on first-line and second-line mPAC treatment choices, including variation across countries. Data are descriptive. Results: A total of 2,565 online patient records were completed by 225 physicians (9 countries; n = 500-504 for France/Germany/Italy/Spain/UK). All patients had completed first-line mPAC treatment and 1,666 had started/completed second-line. At metastatic diagnosis, median age was 64 years and 57.7% was male. At first-line and second-line initiation, median CA19-9/albumin/bilirubin levels were 457U×mL-1/32.0g×L-1/1.30mg×dL-1 and 560U×ml-1/30.0g×L-1/1.30mg×dL-1, respectively. WHO performance status was 0/1/2/3/4/unknown in 14.3%/55.5%/26.9%/2.6%/0.2%/0.5% at first-line initiation and 5.7%/45.9%/41.3%/6.0%/0.8%/0.2%, at second-line initiation. (m)FOLFIRINOX/gemcitabine+nab-paclitaxel/gemcitabine-monotherapy were most frequently used first-line treatments and accounted for 35.6%/25.7%/20.5% of patients. France/UK reported higher (m)FOLFIRINOX and gemcitabine-monotherapy and lower gemcitabine+nab-paclitaxel application [(m)FOLFIRINOX in France/Germany/Italy/Spain/UK: 47.4%/33.5%/27.2%/29.0%/40.1%; gemcitabine+nab-paclitaxel: 10.9%/31.0%/36.4%/32.7%/17.9%; gemcitabine-monotherapy: 26.8%/15.9%/19.8%/17.9%/23.4%]. Other gemcitabine-combinations were applied in 9.6% (France/Germany/Italy/Spain/UK: 7.1%/10.5%/6.2%/10.3%/12.9%): in France/Italy typically combined with oxaliplatin, in Germany with erlotinib, and in UK with capecitabine. FOLFIRINOX was modified upfront (22.2%) relatively more often in UK/Italy versus France/Germany (France/Germany/Italy/Spain/UK: 15.4%/12.5%/32.4%%/22.7%/31.2%). Other 5FU-based regimens were applied in 5.4-9.5%, typically 5FU+oxaliplatin. Second-line 5FU-based (45.0%) and gemcitabine-based (53.3%) treatment choices varied substantially among countries. 5FU-based treatment was lower in France/Germany versus Italy/Spain/UK (France/Germany/Italy/Spain/UK: 31.6%/37.2%/58.1%/52.6%/47.9%). Use of 5FU+oxaliplatin/5FU+irinotecan (17.6%/7.0%) was comparable, except for France (5FU+oxaliplatin: 10.9%) and UK (5FU+irinotecan: 1.6%). 5FU monotherapy (16.7%; mainly capecitabine) was more often prescribed in Italy/Spain/UK (France/Germany/Italy/Spain/UK 9.5%/9.0%/24.4%/23.9%/18.3%). Gemcitabine-based second-line treatment was lower in Italy/Spain versus Germany/France (France/Germany/Italy/Spain/UK: 67.3%/61.6%/38.7%/44.9%/51.1%). Gemcitabine+nab-paclitaxel was applied more often than gemcitabine-monotherapy in Germany/Spain, while in France/UK/Italy gemcitabine-monotherapy was used more. Overall, 17.8% of patients received gemcitabine+nab-paclitaxel (highest in Germany; France/Germany/Italy/Spain/UK: 12.8%/34.8%/11.1%/22.4%/4.5%) and 27.1% gemcitabine-monotherapy (highest in France/UK; France/Germany/Italy/Spain/UK: 50.0%/16.2%/22.6%/12.5%/34.1%). Other gemcitabine-based combinations were used in 8.4% (France/Germany/Italy/Spain/UK: 4.5%/10.5%/5.0%/9.9%/12.5%): in France typically combined with oxaliplatin, in Germany with erlotinib, and in UK with capecitabine. Conclusion: In this large European study, mPAC treatment choices seem overall in line with ESMO recommendations. However, substantial geographical variation was reported between countries. Apart from WHO performance status and comorbidities, first-line treatment choices followed local reimbursement status of individual compounds and showed country-specific preferences. Second-line treatment was also guided by first-line treatment. At the time this research was conducted, no second-line mPAC treatment was approved and over 20 treatments/combinations were reported. A more standardized approach may help improving mPAC treatment outcomes.