Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry.

Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60-89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Neuroendocrine Tumors in Routine Clinical Practice in Germany and Austria.

BACKGROUND: The long-acting somatostatin analog lanreotide autogel is effective in the treatment of patients with neuroendocrine tumors. OBJECTIVE: To evaluate the long-term treatment response in patients with neuroendocrine tumors receiving lanreotide autogel in routine clinical practice. METHODS: Non-interventional, 24-month study in patients with neuroendocrine tumors treated with lanreotide autogel (NCT01840449). RESULTS: Patients (n=80) from 26 centers in Germany and Austria were enrolled. Neuroendocrine tumors were mainly grade 1/2, metastasized, intestinal, and associated with carcinoid syndrome; 88.9% had received previous neuroendocrine tumor treatment. Of those, 84.4% had previous surgery, 18.7% had received octreotide. The primary endpoint, defined by a <50% chromogranin A increase at month 12 compared with the lowest value between baseline and month 3 was achieved by 89.5% patients. Stable disease according to Response Evaluation Criteria in Solid Tumors 1.1 was observed in 76.9 and 75.0% patients at months 12 and 24 of lanreotide treatment, respectively. Mean change of chromogranin A levels from baseline to month 24 was -0.12 × upper limit of normal (95% CI, -0.22; -0.45). In a post hoc analysis, 38.5% of the subgroup of patients with carcinoid syndrome had daily diarrhea at baseline vs. 21.4% at month 24. At baseline, 27.8% of patients received lanreotide 120 mg every 4 weeks vs. 56.7% at month 24. Quality of life data were heterogeneous. No new safety issues arose and/or required further investigation. CONCLUSIONS: Our study reflects routine lanreotide autogel use in patients with advanced/metastatic neuroendocrine tumors. This analysis shows effectiveness with stabilization of disease-related symptoms and good tolerability of lanreotide autogel in clinical practice.

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms.

Owing to its heterogeneity and rarity, management of disseminated marginal zone B-cell lymphoma (MZL) remains largely understudied. We present prospective data on choice of systemic treatment and survival of patients with MZL treated in German routine practice. Of 175 patients with MZL who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) collecting data on systemic treatment, 58 were classified as extranodal MZL of mucosa-associated lymphoid tissue (MALT) and 117 as non-MALT MZL. We analyzed the most commonly used first-line and second-line chemo(immuno)therapies between 2009 and 2016 and examined objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and prognostic factors for survival. Compared to patients with MALT MZL, those with non-MALT MZL more often presented with bone marrow involvement (43% vs. 14%), Ann Arbor stage III/IV (72% vs. 57%) and were slightly less often in good general condition (ECOG = 0; 41% vs. 47%). In German routine practice, rituximab-bendamustine for a median of 6 cycles was the most frequently used first-line (76%) and second-line treatment (36%), with no major differences between MZL subtypes. The ORR for patients encompassing any positive response was 81%. For patients with MALT and non-MALT MZL, respectively, 5-years PFS was 69% (95% CI 52%-81%) and 66% (95% CI 56%-75%), 5-years OS 79% (95% CI 65%-89%) and 75% (95% CI 66%-83%). Cox proportional hazards models showed a significantly increased risk of mortality for higher age in all patient groups. Our prospective real world data give valuable insights into the management and outcome of non-selected patients with MZL requiring systemic treatment and can help optimize therapy recommendations.

Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315).

OBJECTIVES: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the "real-world" setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany. PATIENTS AND METHODS: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1. RESULTS: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4-10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9-9.2) with druggable ALK alterations. CONCLUSION: Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.

Clinical Practice Observation of Trastuzumab in Patients with Human Epidermal Growth Receptor 2-Positive Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.

BACKGROUND: The observational study HerMES collected primary data on effectiveness and safety of trastuzumab in patients with human epidermal growth receptor 2 (HER2)-positive cancer of the stomach or gastroesophageal junction (GEJ) in routine clinical practice, exploring the treatment with trastuzumab, chemotherapy backbones used, and the HER2 testing in a real-world setting in Germany. SUBJECTS, MATERIALS, AND METHODS: This noninterventional study observed patients with histologically confirmed, HER2-positive metastatic adenocarcinoma of the stomach or GEJ, who were treated with trastuzumab according to the physicians' judgement and clinical practice. The observation phase per patient took as long as the duration of the trastuzumab therapy, but for a maximum of 12 months. A subsequent extended follow-up phase lasted until the patient's death or the end of the study, that is, 2 years from start of the follow-up phase of the last patient. All data were analyzed descriptively. RESULTS: Between February 2010 and July 2016, 364 patients were observed at 171 sites throughout Germany. The median overall survival was 14.1 months and the median progression-free survival was 7.9 months. The overall response rate was 43%. Safety was in line with previous reports. This study observed a high diversity of chemotherapy regimens that were combined with trastuzumab. Post hoc subgroup analyses showed differences in outcomes according to the chemotherapy regimen used. CONCLUSION: Trastuzumab treatment in everyday practice as observed in HerMES confirmed the positive results of the pivotal study ToGA in an observational, real-world setting. IMPLICATIONS FOR PRACTICE: Real-world data of trastuzumab treatment of patients with gastroesophageal or gastric metastatic adenocarcinoma confirmed the positive results of the pivotal clinical trial. The observed median overall survival was 14.1 months and the median progression-free survival was 7.9 months. Although recommendations concerning administration of trastuzumab were well implemented, a high diversity of chemotherapy regimens were combined with trastuzumab. Regimens other than the in-label regimens, especially oxaliplatin-based doublets or 5-fluorouracil, leucovorin, oxaliplatin, taxane triplets, were used in 29% of patients. Observation of a second, marginal HER2-positivity population confirmed the benefit of trastuzumab predominantly for well-confirmed human epidermal growth receptor 2 (HER2)-positive tumors and the requirement of reliable HER2 testing.

Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients' preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer.

BACKGROUND: The objective of the IMPROVE study was patients' preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer. METHODS: In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients' preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL). RESULTS: 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first-/second-line, Cap+Bev) and 54.1% and 52.9% (first-/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines. CONCLUSIONS: Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians' preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported. TRIAL REGISTRATION: EudraCT No: 2013-005329-22. Registered on 19 August 20.

Efficacy and safety of irinotecan-based chemotherapy for advanced colorectal cancer outside clinical trials: an observational study.

BACKGROUND: This prospective observational study in typical community-based outpatient clinics evaluated the efficacy and toxicity of weekly and biweekly irinotecan-based chemotherapies and their compatibility depending on age. METHODS: 601 patients with advanced or metastatic colorectal cancer receiving first-, second-, or third-line irinotecan-based therapy were regularly analyzed for response and toxicity until the end of therapy. RESULTS: The median age was 65 (28-87) years, approximately one-third of the patients were ≥70 years old. Of all patients, 405 were treated weekly and 68 biweekly. Median overall survival (OS) for first-line therapy was 26.5 months for the <70-year-old patients and 19.4 months for the ≥70-year-old patients. Toxicities were moderate in all groups. Tumor growth control rates (TCR) and median time to progression (TTP) were marginally better for patients <70 years old. Median TTP was 9.9 months in first-line therapy, 9.8 months after adjuvant therapy, 7.7 months in second-line, and 6.4 months in third-line therapy. CONCLUSIONS: Toxicity and response data from this observational study clearly confirm the positive results from previous clinical studies and show a slight ad-vantage in efficacy for the <70-year-old patients.