Cytoreductive treatment in real life: a chart review analysis on 1440 patients with polycythemia vera

Purpose!#!Patients with polycythemia vera (PV) show an elevated incidence of thromboembolic complications and decreased survival when compared to age-matched healthy individuals. Hypercellularity as indicated by elevated hematocrit, pathophysiological changes induced by the JAK2 driver mutation and cardiovascular risk factors contribute to the increased incidence of thromboembolic events. Higher age and a history of thromboembolic events define a high-risk population of PV patients. Depending on the individual risk profile, phlebotomy or pharmacologic cytoreduction is recommended in combination with low-dose acetylsalicylic acid. Stringent cytoreduction is required for effective risk reduction. However, in recent reports, the rate of thromboembolic complications in PV patients under cytoreductive therapy appears still elevated compared to healthy individuals. This study reports on a chart review to assess for cytoreductive therapy of 1440 PV patients in real life.!##!Methods!#!Forty-two eligible hematologists/oncologists in private practice treating patients with MPN were recruited to participate in a paper-pencil-based survey conducted between January 2019 and March 2020 in Germany. Physicians were asked to report primary documented data obtained from patient charts. Descriptive analyses were conducted to assess for patient characteristics, treatment modalities, risk factors and thromboembolic complications.!##!Results!#!Data were collected from the patient charts of 1440 individuals diagnosed with PV. The patient population was older than those reported in multicenter trials with a median age of 72.2 years at the time of reporting and 63.5 years at diagnosis. Age was the main factor accounting for high-risk status with 84.7% of patients being above the age of 60 followed by thromboembolic complications reported in 21.3% of patients. The use of pharmacologic cytoreduction was highly variable between participating centers with an average of 60.7% and a range of 10.1-100%. Hydroxyurea was the most frequently used drug followed by ruxolitinib, while interferons were reported for a minority of patients. For 35.4% of patients a persistent need for phlebotomy in addition to cytoreductive treatment was reported. Although presence of high-risk criteria and insufficient disease control were reported as main triggers to initiate pharmacologic cytoreduction, 28.1% had elevated hematocrit values (> 45%) and 38.6% showed persistence of elevated leukocyte count (> 10!##!Conclusions!#!Cytoreductive treatment of high-risk PV in real life is highly variable regarding indication for cytoreduction and definition of therapy resistance. This study highlights the need for (i) improved risk stratification for thromboembolic events, (ii) consequent indication of pharmacologic cytoreduction in high-risk PV and (iii) attention to signs of therapy resistance that can trigger an earlier and stringent switch to second line agents

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem