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.

Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile.

Efficacy of anterior odontoid screw fixation in the elderly patient: a CT-based biometrical analysis of odontoid fractures.

In the elderly population, reported union rates with anterior odontoid screw fixation (AOSF) for odontoid fracture (OF) treatment vary between 23 and 93% when using plain radiographs. However, recent research revealed poor interobserver reliability for fusion assessment using plain radiographs compared to CT scans. Therefore, union rates in patients aged ≥60 years treated with AOSF have to be revisited using CT scans and factors for non-union to be analysed. Prospectively gathered consecutively treated patients using AOSF for odontoid fracture with age ≥60 years were reviewed. Medical charts were assessed for demographics, clinical outcomes and complications. Patients' preoperative radiographs and CT scans were analysed to characterize fracture morphology and type, fracture displacement, presence of atlanto-dental osteoarthritis as well as a detailed morphometric assessment of fracture surfaces (in mm(2)). CT scans performed after a minimum of 3 months postoperatively were analysed for fracture union. Those patients not showing CT-based evidence of completely fused odontoid fracture were invited for radiographic follow-up at a minimum of 6 months follow-up. Follow-up CT-scan were studied for odontoid union as well as the number of screws used and the square surface of screws used for AOSF and the related corticocancellous osseous healing surface of the odontoid fragment (in %) were calculated. Patients were stratified whether they achieved osseous union or fibrous non-union. Patients with a non-union were subjected to flexion-extension lateral radiographs and the non-union defined as stable if no motion was detected. The sample included 13 male (72%) and 5 female (18%) patients. The interval from injury to AOSF was 4.1 ± 5.3 days (0-16 days). Age at injury was 78.1 ± 7.6 years (60-87 years) and follow-up was 75.7 ± 50.8 months (4.2-150.2 months). 10 patients had dislocated fractures, 14 had Type II and 4 "shallow" Type III fractures according to the Anderson classification, 2 had stable C1-ring fractures, 8 had displayed atlanto-dental osteoarthritis. Fracture square surface was 127.1 ± 50.9 mm(2) (56.3-215.9 mm(2)) and osseous healing surface was 84.0 ± 6.8% (67.6-91.1%). CT-based analysis revealed osseous union in 9 (50%) and non-union in 9 patients (50%). Union rates correlated with increased fracture surface (P = 0.02). Statistical analysis revealed a trend that the usage of two screws with AOSF correlates with increased fusion rates (P = 0.06). Stability at C1-2 was achieved in 89% of patients. CT scans are accepted as the standard of reference to assess osseous union. The current study offers an objective insight into the union rates of odontoid fractures treated with AOSF using CT scans in consecutive series of 18 patients ≥60 years. Literature serves evidence that elderly patients with unstable OF benefit from early surgical stabilization. However, although using AOSF for unstable OF yields segmental stability at C1-2 in a high number of patients as echoed in the current study, our analysis stressed that using follow-up CT scans in comparison to biplanar radiographs dramatically reduces osseous union rates compared to those previously reported for AOSF.

Olaratumab plus anthracyline in advanced/metastatic soft tissue sarcoma : Data of real-world utilization in Austria.

BACKGROUND: Olaratumab is a humanized monoclonal antiplatelet-derived growth factor receptor alpha antibody that has been approved in combination with doxorubicin for the treatment of patients with metastatic soft tissue sarcoma (STS). The purpose of this retrospective study was to assess the clinical efficacy in STS patients treated with olaratumab in a real-world setting in Austria. METHODS: Retrospectively collected longitudinal data from patients treated between November 2016 and September 2018 at 9 Austrian centers were obtained from the respective medical charts. All patients who received at least one dose of olaratumab were eligible. Parameters of most interest were response rates, progression-free survival (PFS) and overall survival (OS). RESULTS: Altogether 55 patients were included in the analysis. The median age was 58 years. In total, 65.5% (n = 36), 21.8% (n = 12) and 12.7% (n = 7) received olaratumab as first, second or ≥third line treatment, respectively. Olaratumab was administered either in combination with doxorubicin (81.8%, n = 45) or liposomal doxorubicin (16.4%, n = 9); one patient received olaratumab as upfront monotherapy. The median PFS and OS were 2.6 and 11.4 months, respectively. The objective response rate was 11.4% and the disease control rate was 40.9%. CONCLUSION: In this real-world analysis the outcome was less pronounced compared to the results of both the phase Ib/II approval trial and the confirmatory phase III trial. The latter failed to show an improvement in OS and PFS for the doxorubicin/olaratumab combination. As such, olaratumab should not be used anymore in patients with STS.

Female gender may predict response to FOLFIRINOX in patients with unresectable pancreatic cancer: a single institution retrospective review.

FOLFIRINOX is a highly active regimen for the treatment of patients with unresectable pancreatic cancer. However, treatment with FOLFIRINOX is associated with relevant toxicity and predictors for response to therapy are warranted. We retrospectively analyzed 49 patients with unresectable pancreatic cancer treated with FOLFIRINOX in order to evaluate a possible predictive role of clinical parameters and tumor characteristics for response to chemotherapy. Tumor samples were characterized histopathologically before treatment and expression of p53 and Ki67 was analyzed using automated immunohistochemistry. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. The overall objective response rate was 55.1%, the disease control rate was 70.6%. Female gender was associated with a significantly higher disease control rate of 91.7 compared to 48.0% in male patients (p=0.001) which reached 100% in female patients when primarily treated compared to treatment after surgical resection and relapse (77.8%, p=0.057). For all patients median PFS was 3.5 months (95% CI, 2.7-4.3 months) and median OS was 13 months (95% CI, 9.4-16.6 months). Female patients showed a tendency towards a longer median PFS (5.0 months, 95% CI, 3.6-6.4 months) compared to males (3.0 months, 95% CI, 2.4-3.6 months) (p=0.099). Serum levels of CA19.9 and CEA were significantly higher in female patients compared to male patients (p=0.037, p=0.05). Tumors of patients with response to FOLFIRINOX showed a higher expression level of p53 and Ki67 as well as higher serum levels of CA19.9 compared to non-responders, which was statistically not significant. Our study indicates that female gender is a positive predictor for therapy response to FOLFIRINOX in patients with unresectable pancreatic cancer. Female gender in turn was associated with increased levels of tumor markers CEA and CA19.9 and patients with higher serum levels of CA19.9 were more responsive to FOLFIRINOX.

Hypertension as a predictive marker for bevacizumab in metastatic breast cancer: results from a retrospective matched-pair analysis.

BACKGROUND: Several phase-III studies have shown improvements in terms of progression-free survival (PFS) with bevacizumab when added to chemotherapy in advanced breast cancer. However, the extent of improvement varied and none of the trials showed benefit in terms of overall survival (OS). PATIENTS AND METHODS: All patients with metastatic breast cancer treated with bevacizumab at our Institution between 2005 and 2011 were retrospectively analyzed. A control group was matched according to the following variables: receptor status, treatment line, type of chemotherapy, presence of visceral disease and age. RESULTS: All 212 patients were evaluable for toxicity, and 198 for response; 430 controls allowed a complete matching for 85 bevacizumab-treated patients. The addition of bevacizumab to chemotherapy significantly prolonged PFS (9.3 vs. 7.6 months, hazard ratio [HR]=0.70, 95% confidence interval [CI]=0.51-0.97, p=0.031) and OS (28.9 vs. 22.6 months, HR=0.67, 95% CI=0.45-0.99, p=0.043). Clinical benefit rate (overall response rate + stable disease for at least six months) was significantly better in the bevacizumab group (75% vs. 59%, p=0.002), while ORR did not differ significantly (48% vs. 35%, p=0.21). Patients developing hypertension during treatment had a more favourable outcome (PFS 13.7 vs. 6.6 months, HR=0.34, 95% CI=0.23-0.49 p<0.001; 2-year OS 78% vs. 30%, HR=0.20, 95% CI=0.12-0.35, p<0.001). CONCLUSION: Bevacizumab in addition to chemotherapy prolonged PFS and OS in a non-selected, partly intensively pre-treated breast cancer population. Hypertension induced by bevacizumab predicted therapy efficacy.