Head-to-head comparison of treatment sequences in advanced pancreatic cancer-Real-world data from the prospective German TPK clinical cohort study.

There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess real-world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab-paclitaxel (GEMNAB; n = 938) as palliative first-line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health-related quality of life (HRQoL) between three common first- to second-line treatment sequences, adjusting for time-varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5-fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5-fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor-risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5-fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%-confidence intervals. The estimated real-world effectiveness of the three treatment sequences evaluated were largely comparable. Poor-risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient-reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.

Spotlight on the real-world treatment of CML pts in Germany: a retrospective survey in private oncology practices.

Clinical trials in chronic myeloid leukemia (CML) are usually carried out in specialized centers whereas primary care for patients (pts) with CML is mainly provided by local oncology practices. The aim of this study was to assess treatment practices in pts with CML in the setting of private oncology practices in Germany. We collected data of 819 pts with a confirmed diagnosis (dx) of CML in 2013 or later from 43 practices. At dx, 84.2% (n=690) and 9.4% (n=77) of pts were in chronic or accelerated phase, 0.7% (n=6) had a blast crisis. Molecular monitoring was provided by EUTOS certified laboratories in 87.7% of pts. Typical BCR::ABL1 transcripts were detected in 86.6% (n=709). Molecular response was assessed after 2.8, 6.0, 9.4 and 12.9 m (mean) after start of treatment. Of the pts with available data, 11.1% did not achieve early molecular response and at 18 m, 83.7% had at least a major molecular response. 288 (35.2%) of pts switched to 2nd line (2L) treatment after a mean of 21.0 months. Reasons for 2L treatment were side effects in 43.4% and suboptimal response or failure in 31.4% of pts. 106 pts went on to third line (3L) treatment. 36.8 % of pts switched to and 92.8 % of pts still on 3L treatment achieved BCR::ABL1IS ≤1% at 12 m. In conclusion, in Germany pts with CML are routinely monitored by qPCR and good responses are achieved in the majority. Treatment changes are mainly due to adverse events rather than suboptimal responses.

Fludarabine, cyclophosphamide, and rituximab as first-line treatment in patients with chronic lymphocytic leukemia: A long-term analysis of the German CLL Study Group (GCLLSG) registry.

Long-term data of chronic lymphocytic leukemia (CLL) patients with favorable risk who were treated with fludarabine, cyclophosphamide, and rituximab (FCR) within clinical trials show good efficacy. We here report long-term data collected within the GCLLSG registry. Altogether, 417 CLL patients who received first-line treatment with FCR were analyzed, of which 293 (70.3%) were treated outside of clinical trials. The median observation time from first-line was 95.8 (interquartile range 58.7-126.8) months. Focusing on data of 194 (46.5%) patients who received FCR first-line treatment after 2013 (start of data collection within GCLLSG registry), responses were documented in 85% of the patients, non-responses in 15%, and for 3.6% the assessment was missing. Median event-free survival (EFS, time until disease progression, subsequent treatment, or death) was 60.2 months with a 5-year EFS-rate of 50.6%. Patients with higher-risk disease, characterized by unmutated IGHV (N = 78), had a median EFS of 45.4 months with a 5-year EFS rate of 36.3%, while the median EFS was 77.5 months with a 5-year EFS rate of 60.3% in patients with mutated IGHV (N = 40). Median overall survival was not reached with a 5-year survival rate of 92.7%. In summary, first-line FCR was associated with long EFS, especially in patients exhibiting a mutated IGHV status.

Treatment with idelalisib in patients with chronic lymphocytic leukemia - real world data from the registry of the German CLL Study Group.

Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at www.clinicaltrials.gov as # NCT02863692) meeting the predefined criteria of a confirmed diagnosis of CLL and being treated with idelalisib containing regimens outside clinical trials were considered. 11 patients were treatment naïve (13.6%) and 70 patients (86.4%) pretreated. Patients had median of one prior therapy line (range 0-11). Median treatment duration with idelalisib was 5.1 months (range 0-55.0 months). Of 58 patients with documented treatment outcome, 39 responded to idelalisib containing therapy (67.2%). Patients treated with the BTKi ibrutinib as last prior treatment prior to idelalisib responded in 71.4% compared to a response rate of 61.9% in patients without prior ibrutinib. Median event free survival (EFS) was 15.9 months with a 16 versus 14 months EFS in patients with ibrutinib as last prior treatment or not, respectively. Median overall survival was 46.6 months. In conclusion, treatment with idelalisib appears to have a valuable impact in patients being refractory to prior ibrutinib therapy even though there are limitations in our analysis due to the low number of patients included.

Results from the prospective German TPK clinical cohort study: Treatment algorithms and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma.

Pancreatic cancer is a highly lethal malignancy. Developments in recent years have broadened our therapeutic armamentarium. Novel drugs such as nab-paclitaxel, liposomal irinotecan and chemotherapy regimens such as FOLFIRINOX have been successfully tested in clinical trials. Data on patients outside of clinical trials are scarce but necessary to assess and improve the standard of care. We present data on treatment and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma. Between February 2014 and June 2017, patients were recruited by 104 sites at start of first-line therapy into the ongoing, prospective clinical cohort study TPK (Tumour Registry Pancreatic Cancer). As first-line therapy, 89% of patients received one of the three treatment regimens: gemcitabine monotherapy (23%), nab-paclitaxel plus gemcitabine (42%), or FOLFIRINOX (24%). The corresponding subgroups differed: Patients receiving gemcitabine monotherapy were older and more comorbid (median age 78 years, 73% ECOG ≥ 1) than patients receiving nab-paclitaxel plus gemcitabine (median age 71, 64% ECOG ≥ 1) or patients receiving FOLFIRINOX (median age 60, 52% ECOG ≥ 1). At least 40% of patients died before receiving second-line treatment. First-line progression-free survival was 4.6 months (95% CI: 3.7-5.2) for gemcitabine, 5.6 months (95% CI: 5.0-6.2) for nab-paclitaxel plus gemcitabine, and 6.3 months (95% CI: 5.5-6.9) for FOLFIRINOX. Our data represent the treatment reality in a German community setting. Although there are no stringent inclusion criteria for our cohort study, overall survival is comparable to that reported by randomised clinical trials.

Bendamustin-Rituximab Combination Is a Safe and Effective, Ambulatory Treatment for Elderly Patients with Chronic Lymphocytic Leukemia: Retrospective Real-world Analysis by Age from a German Registry and Review of the Literature.

BACKGROUND: Treatment recommendations in chronic lymphocytic leukemia (CLL) are based upon selected, otherwise healthy study populations mostly under 72 years of age. The Project group Internistic Oncology (PIO) embarked on an analysis of the 'real-world' safety and efficacy of bendamustine with and without rituximab in unselected outpatients. PATIENTS AND METHODS: A multicenter, open-label, prospectively stratified, retrospective study was conducted to determine routine feasibility, toxicity, and response rates obtained by bendamustine with and without rituximab in a random population of mostly elderly patients with CLL. Records were obtained from 775 patients with CLL from 60 private medical oncology practices. Informed consent was obtained prior to study participation. The median observation time was 28 months. Patients were stratified according to age, and treatment. Response criteria and statistics followed international guidelines adopted by the "German Chronic Lymphocytic Leukemia Study Group". RESULTS: Overall, 57.5% of patients were over 70 (range=36-95) years old. Eastern Cooperative Oncology Group performance status and age influenced the total dose given, decreasing by 20% between ECOG 0 and 3, and by 15% above 80 years old. Response rates did not differ between the ages of 60 to 80 years, with an overall remission rate for bendamustine of 83%, and for the combination therapy of 89%, decreasing above the age of 80 years. Febrile neutropenia occurred in 25% of 775 patients, and grade 3 or 4 non-hematological adverse events in 9.55% (n=74), not interfering with the treatment. CONCLUSION: Bendamustine with and without rituximab was associated with high activity and tolerability, irrespective of age and risk factors. The median overall survival was 64 months with a 3-year survival rate of 72%; progression-free survival was 30.6 months, and the 3 year PFS was 43%. The good tolerability and feasibility of bendamustine with and without rituximab, in particular for the elderly population with CLL argues for it being a safe outpatient treatment.

Pattern formation and mass transfer under stationary solutal Marangoni instability.

According to the seminal theory by Sternling and Scriven, solutal Marangoni convection during mass transfer of surface-active solutes may occur as either oscillatory or stationary instability. With strong support of Manuel G. Velarde, a combined initiative of experimental works, in particular to mention those of Linde, Wierschem and coworkers, and theory has enabled a classification of dominant wave types of the oscillatory mode and their interactions. In this way a rather comprehensive understanding of the nonlinear evolution of the oscillatory instability could be achieved. A comparably advanced state-of-the-art with respect to the stationary counterpart seemed to be out of reach a short time ago. Recent developments on both the numerical and experimental side, in combination with assessing an extensive number of older experiments, now allow one to draw a more unified picture. By reviewing these works, we show that three main building blocks exist during the nonlinear evolution: roll cells, relaxation oscillations and relaxation oscillations waves. What is frequently called interfacial turbulence results from the interaction between these partly coexisting basic patterns which may additionally occur in different hierarchy levels. The second focus of this review lies on the practical importance of such convection patterns concerning their influence on mass transfer characteristics. Particular attention is paid here to the interaction between Marangoni and buoyancy effects which frequently complicates the pattern formation even more. To shed more light on these dependencies, new simulations regarding the limiting case of stabilizing density stratification and vanishing buoyancy are incorporated.