Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer: Long-Term Follow-Up of the ASSO-LM1 Trial.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.

Geriatric Assessment of Older Patients Receiving Trabectedin in First-Line Treatment for Advanced Soft Tissue Sarcomas: The E-TRAB Study from The German Interdisciplinary Sarcoma Group (GISG-13).

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.

German, Austrian, and Swiss guidelines for systemic treatment of gastric cancer.

The updated edition of the German, Austrian and Swiss Guidelines for Systemic Treatment of Gastric Cancer was completed in August 2023, incorporating new evidence that emerged after publication of the previous edition. It consists of a text-based "Diagnosis" part and a "Therapy" part including recommendations and treatment algorithms. The treatment part includes a comprehensive description regarding perioperative and palliative systemic therapy for gastric cancer and summarizes recommended standard of care for surgery and endoscopic resection. The guidelines are based on a literature search and evaluation by a multidisciplinary panel of experts nominated by the hematology and oncology scientific societies of the three involved countries.

Systemic treatment of patients with locally advanced or metastatic cholangiocarcinoma - an Austrian expert consensus statement.

Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting. Regarding the use of chemotherapy in the second line, positive phase III data could only be generated for FOLFOX. The evidence base for nanoliposomal irinotecan (Nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) is contradictory. After the failure of first-line treatment, targeted therapies can be offered if the molecular targets microsatellite instability-high (MSI-H), IDH1, FGFR2, BRAF V600E, and NTRK are detected. These targeted agents are generally preferable to second-line chemotherapy. Broad molecular testing should be performed, preferably from tumor tissue, at the initiation of first-line therapy to timely identify potential molecular targets.

LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study.

Background: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM. Methods: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS. Results: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively. Conclusions: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

Treatment Algorithm for Patients With Gastric Adenocarcinoma: Austrian Consensus on Systemic Therapy - An Update.

Over the last decade, therapeutic options for patients with gastric cancer have improved significantly. However, despite these recent advances, mortality is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Immune checkpoint inhibitors as well as targeted treatments such as HER2-directed therapies and antiangiogenic agents contribute to improved patient prognosis. Herein, we present the updated version of an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and adenocarcinoma of the lower gastroesophageal junction, including those with human epidermal growth receptor 2 (HER2) overexpression, microsatellite instability, programmed death-ligand 1 (PD-L1)-positive disease, and claudin 18.2 positivity. The consensus considers the curative setting as well as first-line and later-line systemic treatment options in advanced disease. For HER2-positive disease, HER2 testing is discussed in addition to a review of first-line and later-line therapies. Potential future therapies are also listed, with a focus on targeted [e.g., fibroblast growth factor receptor 2 (FGRF2)-directed] treatments that might provide a further step forward in the management of patients with gastric cancer.

Patterns of care for relapsed oesophageal cancer after initial curative trimodality therapy: Long-term follow-up of the SAKK 75/08 trial.

BACKGROUND: Recurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. METHODS: We analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. RESULTS: Among 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. CONCLUSIONS: Recurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.

Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.

BACKGROUND/AIM: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS: Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. RESULTS: Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION: Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients.

New entity of microsecretory adenocarcinoma of salivary glands: first case with recurrence and metastases - proof of malignancy.

Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases.

Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort.

BACKGROUND: Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing. METHODS: In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort. RESULTS: In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4-2.8) and 6.3 (95% CI: 3.3-9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 (p = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity. CONCLUSIONS: Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.

Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: Analysis of a multicentre, prospective, non-interventional study.

BACKGROUND: Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine. METHODS: Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing. RESULTS: A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy. CONCLUSION: This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. CLINICALTRIALS. GOV REGISTRATION: NCT02555813. AUSTRIAN NIS REGISTRY: NIS005071.

Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper.

BACKGROUND: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%. SUMMARY: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.

REGO-ACT: assessment of physical activity during treatment with regorafenib for metastatic colorectal cancer.

BACKGROUND: A frequent side effect of the multikinase inhibitor regorafenib is fatigue. Physical activity has shown potential in reducing cancer-related fatigue. METHODS: This non-interventional pilot study assessed physical activity levels of metastatic colorectal cancer (mCRC) patients treated with regorafenib based on median daily step counts measured at 1­week intervals using a pedometer. The study further evaluated relations between physical activity levels and fatigue, quality of life (QoL) and progression-free survival. RESULTS: Pedometer data were available for 22 out of 25 enrolled patients. The numbers of days with available pedometer data ranged from 6 to 100 days. The overall median daily step count was 2357 (range 10-14,931), with substantial interindividual and intraindividual variations. Interindividual median weekly step counts were in the range of 5000-7000 in some, 2000-3000 in others, and several hundreds or less in a few patients. Intraindividual daily step counts also varied by several thousands of steps. Step counts in weeks in which patients reported fatigue were well within the range of or even higher than step counts in adjacent weeks, indicating a lack of correlation. The risk of disease progression was also independent of median weekly step counts; however, significant correlations were seen between QoL and step counts. CONCLUSION: Despite the severity of their disease patients showed remarkable levels of walking activity. In view of the highly individual activity levels, exercise prescriptions for seriously ill patient populations should be personalized to the specific needs and preferences of each individual patient.

Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer-Results from the AGMT GASTRIC-5 Registry.

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870-24,530) vs. 6.9 months (95% CI: 3.980-9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.

The AST/ALT (De Ritis) ratio predicts clinical outcome in patients with pancreatic cancer treated with first-line nab-paclitaxel and gemcitabine: post hoc analysis of an Austrian multicenter, noninterventional study.

BACKGROUND: The pretreatment De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)] has been shown to be an adverse prognostic marker in various cancer entities. However, its relevance to advanced pancreatic ductal adenocarcinoma (PDAC) has not yet been studied. In the present study we investigated the AST/ALT ratio as a possible predictor of treatment response and disease outcome in patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel. METHODS: A post hoc analysis of a prospective, multicenter, noninterventional study was performed. A total of 202 patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel for whom the AST/ALT ratio was measured were included in this analysis. RESULTS: Median and 1-year progression-free survival estimates were 4.8 months and 5.1%, respectively in patients with an AST/ALT ratio above the 75th percentile of its distribution, and 6.0 months and 18.7%, respectively in patients with an AST/ALT ratio less than or equal to this cutoff, respectively (log-rank p = 0.004). In univariable Cox regression, a doubling of the AST/ALT ratio was associated with a 1.4-fold higher relative risk of progression or death [hazard ratio = 1.38, 95% confidence interval (CI): 1.06-1.80, p = 0.017]. The prognostic association was also found in multivariable analysis adjusting for Eastern Cooperative Oncology Group performance status and lung metastases (hazard ratio per AST/ALT ratio doubling = 1.32, 95% CI: 1.00-1.75, p = 0.047). In treatment response analysis, a doubling of the AST/ALT ratio was associated with a 0.5-fold lower odds of objective response (odds ratio = 0.54, 95% CI: 0.31-0.94, p = 0.020). CONCLUSIONS: The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.

High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08.

BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1-3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m2, cisplatin 75 mg/m2 followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7-12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0-8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1-2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010.

Patterns of care in metastatic pancreatic cancer: patient selection in clinical routine.

BACKGROUND: The management of patients with metastatic pancreatic cancer (mPC) is challenging, and the optimal treatment strategy is debated among experts. In an attempt to identify treatment decision criteria and to investigate variations in the first-line management of this disease, we performed an analysis of treatment algorithms among experts in the field of pancreatic cancer. The aim of this study was to identify relevant criteria in the complex process of patient selection and decision making for the management of mPC patients. METHODS: Experts from the ABCSG (Austrian Breast and Colorectal Cancer Study Group) Pancreatic Cancer Club were contacted and agreed to participate in this analysis. Eight experts from seven centers in Austria provided their decision algorithms for the first-line treatment of patients with mPC. Their responses were converted into decision trees based on the objective consensus methodology. The decision trees were used to identify consensus and discrepancies. RESULTS: The final treatment algorithms included four decision criteria (performance status, age, comorbidities, and symptomatic disease) and six treatment options: mFOLFIRINOX, gemcitabine + nab-paclitaxel, gemcitabine mono, 5-FU mono, gemcitabine/erlotinib, and best supportive care (BSC). CONCLUSIONS: We identified consensus for the treatment of young and fit patients with mFOLFIRINOX. With higher age and reduced performance status, gemcitabine + nab-paclitaxel was increasingly used. For patients with Eastern Co-operative Oncology Group Performance Status (ECOG PS) 4, BSC was the treatment of choice. Among experts, different decision criteria and treatment options are implemented in clinical routine. Despite multiple options in current recommendations, a consensus for specific recommendations was identified.

Treatment Algorithm for Patients With Gastric Adenocarcinoma: An Austrian Consensus on Systemic Therapy.

Despite recent advances in the treatment of gastric cancer, mortality related to this disease is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Targeted treatments that include anti-angiogenic agents and the advent of immunotherapies can contribute to improved patient prognosis. Herein, we present an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and lower gastroesophageal junction, including those with human epidermal growth factor receptor 2 (HER2)-positive disease. The consensus considers the curative setting, as well as first-line to late-line systemic treatment options in the palliative setting. For HER2-positive disease, first-line and second-line therapies are discussed, as well as HER2 testing. Potential future therapies are also listed, with a focus on anti-angiogenic treatments and checkpoint inhibition, that might provide a further step forward in the management of patients with gastric cancer.

Chemotherapy, Still an Option in the Twenty-First Century in Metastatic Colorectal Cancer?

Substantial improvements have been made in the systemic treatment of colorectal cancer over the last two decades. Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has been constantly increased and the most recent first-line studies exceeded the 30-month median overall survival. The standard first-line regimen for mCRC is a combination of chemotherapy plus a biological agent either targeting the main angiogenic growth factor vascular endothelial growth factor (VEGF) via Bevacizumab or by antibodies targeting the epidermal growth factor receptor (EGRF) via Panitumumab or Cetuximab. Recent improvements have been shown in the efficacy of the biological agent by stratifying these agents according to the primary tumor location. In this context EGFR-inhibitors showed improved OS when used first-line in tumors derived from the left-sided colon or rectum, while tumor sidedness was not predictive for anti-VEGF-antibodies. Furthermore, the biological activity of anti-EGFR antibodies is restricted to tumors with a rat sarcoma virus (RAS)-wild-type genotype but not RAS-mutated tumors. The RAS-mutation status is not predictive for VEGF-inhibitors. Recent developments in the molecular characterisation of tumor cells led to the development of specific so called targeted therapies in colorectal cancer.

Efficacy and safety of regorafenib compared to placebo and to post-cross-over regorafenib in advanced non-adipocytic soft tissue sarcoma.

INTRODUCTION: The placebo-controlled phase-2 REGOSARC trial demonstrated the efficacy of regorafenib in patients with leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcoma but not in liposarcoma. Patients initially allocated to placebo were allowed to receive regorafenib after progression. We report here an updated analysis of the trial including evaluation of regorafenib activity after cross-over. METHODS: From June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts. Median follow-up is now 32.4 months. Benefit of regorafenib versus placebo in terms of progression-free survival (PFS) and overall survival (OS) from randomisation was estimated by hazard ratio (HR) in Cox models. In the placebo arm, intra-patient benefit of regorafenib after cross-over was evaluated by the growth modulation index (GMI) (GMI was here, for each patient, PFS after cross-over regorafenib divided by PFS with placebo). Furthermore, the activity of delayed (after cross-over) versus early (at study entry) regorafenib was evaluated by comparing PFS after cross-over to regorafenib to PFS after randomisation in the regorafenib arm. RESULTS: PFS benefit of regorafenib as compared to placebo was confirmed with longer follow-up (HR = 0.50; 95% CI: 0.35-0.71; p < .0001). OS was not statistically significant different (HR = 0.78; 0.54-1.12; p = .18). This finding may partially be explained by the fact that 55/68 patients who progressed on placebo (81%) received cross-over Regorafenib after progression: 59% of them had a GMI ≥ 1.3 (95% CI, 45-71%). Delayed start of regorafenib was associated with a statistically non-significant shorter PFS as compared to early treatment (HR = 1.21; 0.84-1.73; p = .30) without impact on OS. CONCLUSIONS: Observed PFS confirms that regorafenib warrants further clinical investigation in refractory non-adipocytic sarcomas.