Biosimilar Erythropoietin Alpha Is Effective As Originator Erythropoietin Alpha Plus Liposomial Iron and B12 and Folates in Patients with Refractory Anemia: A Retrospective Real-Life Approach

Blood Journal. Dec 2014. 124(21): 4880-488

Transforming growth factor alpha, amphiregulin and cripto- 1 are frequently expressed in advanced ovarian carcinomas

The expression of transforming growth factor alpha (TGFalpha), amphiregulin (AR) and cripto-1 (CR-1) was assessed by immunohistochemistry in 83 specimens (59 primary ovarian tumors and 24 extra-ovarian carcinomas) that were obtained from 68 ovarian carcinoma patients. Within the 59 primary tumors, 54 (92%) expressed immunoreactive TGFalpha, 45 (76%) expressed AR, and 28 (47%) expressed CR-1. The expression of AR and CR-1 mRNAs in the ovarian carcinomas was also demonstrated by RT-PCR analysis. Seventeen extra-ovarian specimens (71%) were found to express CR-1, whereas AR and TGFalpha were expressed respectively in 21 (87%) and 22 (92%) extra-ovarian tissues. In 15 cases for whom both ovarian and extra-ovarian tissues were available, a statistically significant higher expression of CR-1 was found in extra-ovarian specimens. A statistically significant correlation was found between AR expression in the ovarian carcinomas and both low grade and low proliferative activity. Finally, expression of TGFalpha was predictive of longer progression-free survival. These data strongly suggest that the EGF-related peptides might be involved in the pathogenesis and outcome of human ovarian cancer

FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: A prospective study

Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy.

ABSTRACT Background Chemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described. Objective To examine the incidence, duration, and reversibility of arthralgia. Patients and methods A retrospective analysis was performed to describe the occurrence and outcome of arthralgia in 114 patients with advanced ovarian cancer, given first-line treatment with a combination of carboplatin, paclitaxel, and bevacizumab. Statistical analysis was performed to investigate a possible prognostic role of arthralgia, with progression-free survival as endpoint. Results 47 of 114 patients (41%) developed arthralgia during therapy. All patients had grade 1 or grade 2 arthralgia. Toxicity persisted after the end of bevacizumab in 17/47 patients (36%). Median progression-free survival for patients without arthralgia was 18 months (95% CI 14 to 24) compared with 29 months (95% CI 21 to not reached) for patients experiencing arthralgia (p=0.03). In order to avoid possible biases related to treatment duration, a multivariable Cox proportional hazards model including toxicity as a time dependent variable and age, stage, and residual disease after primary surgery was performed. In this model no variable showed a statistically significant association with progression-free survival. Conclusion A high incidence of arthralgia (41%) was found and although rogression-free survival was worse for those patients who developed arthralgia, this was not maintained on multivariate analysis. Guidelines for treatment of this adverse event are needed

Immunotherapy and Sonpavde score validation in advanced upper tract urothelial carcinoma: a retrospective study by the Italian Network for Research in Urologic-Oncology

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8-2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6-8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy >= 3 months) split the patients into three groups (0 vs 1 vs 2-4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process

Results of a Phase II Study of Short-Course Accelerated Radiation Therapy (SHARON) for Multiple Brain Metastases

Objectives: To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Materials and Methods: A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of 643. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. Results: Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to have recursive partitioning analysis class 3 disease. Grade 1-2 acute neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%) experienced neurological grade 3 acute toxicity. With a median follow-up time of 6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed. Seventeen of 27 symptomatic patients showed an improvement or resolution of baseline symptoms (overall palliative response rate: 63.0%; 95% confidence interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7 mo). Conclusions: Short-course accelerated whole brain radiotherapy of 18 Gy in twice daily fractions for 2 consecutive days is tolerated and effective in terms of symptom relief and median survival time. These results justify a phase III comparison against the standard-of-care in this patient population (30 Gy in 10 fractions)

READY: Real-world data from an Italian compassionate use program of avelumab first-line maintenance (1LM) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC)

Background: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1) 1LM plus best supportive care (BSC) in patients (pts) with la/mUC whose disease did not progress after 1L platinum-based chemotherapy (PBC) significantly extended overall survival (OS) vs BSC alone, and it is now recommended internationally as standard of care with level 1 evidence. We report real-world descriptive pt characteristics and outcomes data from a large, multicenter, Italian compassionate use program (CUP) assessing avelumab 1LM in pts with la/mUC. Methods: This prospective, noninterventional CUP was initiated on Jan 18, 2021, to provide early access to avelumab before reimbursement by the Italian Medicines Agency for pts with la/mUC. Avelumab was provided upon physician request and after approval by local ethics committees in accordance with the Italian compassionate use regulation. Avelumab 800 mg IV was administered every 2 weeks per local prescribing information to adult pts aged ≥18 years with la/mUC who were progression-free following PBC (4-6 cycles, starting 4-10 weeks after last dose of PBC). Pts who had a relapse within 12 months of prior adjuvant or neoadjuvant systemic therapy, including immune checkpoint inhibitors, were not eligible. Results: As of Aug 16, 2022, 464 pts (78.4% male, 21.6% female) were included from 140 Italian centers from Jan 2021-Mar 2022. Median age at inclusion was 70 years (IQR, 63-76 years). At the start of 1L PBC, 346 pts (73.9%) had metastatic disease and 40 (8.6%) had unresectable locally advanced disease (disease stage not defined [N/D] in 78 pts [16.8%]). ECOG PS was 0 in 321 pts (69.2%), 1 in 140 (30.2%), and N/D in 3 (0.7%). Primary tumor site was upper tract in 148 pts (31.9%) and lower tract in 309 (66.6%) (N/D in 7 [1.5%]). 1L PBC comprised carboplatin + gemcitabine in 241 pts (51.9%), cisplatin + gemcitabine in 214 (46.1%), and other PBC in 9 (1.9%); 225 pts (48.5%) received 4 cycles of PBC, 54 (11.6%) received 5 cycles, and 177 (38.2%) received 6 cycles (other or N/D in 8 [1.7%]). Complete response to 1L PBC was achieved in 51 pts (11.0%), partial response in 266 (57.3%), and stable disease in 147 (31.7%). For 391 pts currently evaluable for OS and progression-free survival (PFS) from the start of avelumab, the 12-month OS rate was 69.1% (95% CI, 64.4%-73.6%), while median OS was not reached. The 12-month PFS rate was 38.9% (95% CI, 34.0%-43.7%) and median PFS was 6.6 months (95% CI, 5.6-8.9 months). Grade 3-4 adverse events occurred in 33 pts (7.1%). Conclusions: This CUP included a large pt population representative of daily clinical practice in 140 Italian oncology centers and the results are consistent with those of previous studies. Overall, these real-world data strengthen the findings of JAVELIN Bladder 100 and provide further support for avelumab 1LM as a standard of care in eligible pts with la/mUC

Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors. Pathways connected to tissue growth and angiogenesis might have been associated with reduced survival benefit. Individual biomarkers did not comprehensively identify patients who could benefit from therapy; however, multi-parameter models incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility. These results characterize the complex biologic pathways underlying survival benefit from immune checkpoint inhibition in advanced urothelial cancer and suggest that multiple biomarkers might be needed to identify patients who would benefit from treatment