scholarly journals Axitinib as a third or further line of treatment in renal cancer. A single institution experience

2020 ◽  
Author(s):  
Giorgos Tsironis ◽  
Michalis Liontos ◽  
ANASTASIOS KYRIAZOGLOU ◽  
Konstantinos Koutsoukos ◽  
Anna Tsiara ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Histologic Type ◽  
Line Treatment ◽  
Second Line ◽  
Toxicity Profile ◽  
Single Institution ◽  
Real World Data ◽  
Therapeutic Algorithm ◽  
Effective Option ◽  
Recent Developments

Abstract Background: Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically. Methods: Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Statistical analysis was performed with SPSS, including the available clinicopathological data of the patients included. Results: Axitinib was found to be active in patients who received this treatment beyond second line. The toxicity profile of this regimen did not reveal any unknown adverse events. Conclusions: Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.

scholarly journals Axitinib as a third or further line of treatment in renal cancer. A single institution experience

2020 ◽  
Author(s):  
Giorgos Tsironis ◽  
Michalis Liontos ◽  
ANASTASIOS KYRIAZOGLOU ◽  
Konstantinos Koutsoukos ◽  
Anna Tsiara ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Survival Outcomes ◽  
Histologic Type ◽  
Line Treatment ◽  
Second Line ◽  
Single Institution ◽  
Real World Data ◽  
Therapeutic Algorithm ◽  
Effective Option ◽  
Recent Developments

Abstract Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically. Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.

scholarly journals P469 Stay in class or switch out of class after anti-TNF failure in inflammatory bowel disease (IBD). Real-world data from a large district general hospital

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S414-S414
Author(s):  
H Johnson ◽  
S Vythilingam ◽  
S McLaughlin
Keyword(s):  
Clinical Remission ◽  
Disease Type ◽  
Line Treatment ◽  
Second Line ◽  
Real World Data ◽  
Effective Treatment Option ◽  
Significant Cost ◽  
Third Line ◽  
Biologic Drug ◽  
Third Line Treatment

Abstract Background Biosimilar infliximab (IFX) and adalimumab (ADA) are well-proven cost-effective anti-TNF drugs in IBD; in our practice, the majority of patients with IBD receive IFX or ADA first line. Since the introduction of Vedolizumab (VED) and Ustekinumab (UST) some have recommended switching out of class after failing a single anti-TNF. This practice has significant cost implications. To establish the outcome of treatment response in patients treated with a second anti-TNF agent after anti-TNF failure compared with the outcome of patients treated with VED and UST after anti-TNF failure. Methods We maintain a prospective IBD database. We searched our database for the outcomes of patients who failed their first anti-TNF drug but were in a clinical remission 6 months after changing to a second or third biologic drug. Disease type, age, gender and response to their second and third biologic drug were recorded. Clinical remission was defined as off steroids with calprotectin <250 and no symptoms of active IBD. Results Two hundred and eighty-seven patients were identified. One hundred and forty (48.8%) were male. Mean age was 43.2 (range 18–94). Disease type was 75 (26%) UC, 210 (73.2%) CD, 2 (0.7%) IBD-U. One hundred and ninety-three patients received IFX 1st line, 118 (40%) failed. Of these 84 (72%) received ADA, 28 (24%) VED and 6 (5%) UST second line. Remission with second-line treatment was achieved in 58 (69%); ADA, 18 (64%); VED, 6 (100%); UST. Remission with third line treatment; was achieved in 6 (100%); VED; 5 (100%); UST. Ninety-four patients received ADA 1st line, 33 (35%) failed. Of these 11 (33%) received IFX, 10 (30%) VED and 8 (24%) UST second line. Remission with second-line treatment was achieved in 6 (55%); IFX, 10 (100%); VED and 8 (100%); UST. Remission with third line treatment; was achieved in 1 (100%); VED, 4 (100%); UST. Conclusion Our data suggest that treatment with ADA after IFX failure is an effective treatment option whereas IFX treatment after ADA failure is less effective. It is interesting that the majority of those who failed the anti-integrin treatment second line responded to third line ADA. These data are consistent with earlier anti-TNF studies including GAIN (Gauging Adalimumab efficacy in Infliximab Non-responders) and SWITCH (Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial) which demonstrated that anti-TNF failure is not a class effect. We recommend prescribing a second anti-TNF after anti-TNF failure in preference to using an anti-integrin second line. This practice will lead to significant cost savings for the health care economy.

scholarly journals New frontiers in the medical management of gastrointestinal stromal tumours

2019 ◽  
Vol 11 ◽  
pp. 175883591984194 ◽  
Author(s):  
Alessandro Mazzocca ◽  
Andrea Napolitano ◽  
Marianna Silletta ◽  
Mariella Spalato Ceruso ◽  
Daniele Santini ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Novel Therapies ◽  
Second Line ◽  
Clinical Testing ◽  
Mechanisms Of Resistance ◽  
Gastrointestinal Stromal Tumours ◽  
Molecular Events ◽  
Therapeutic Algorithm ◽  
History Of ◽  
Third Line

The tyrosine kinase inhibitor (TKI) imatinib has radically changed the natural history of KIT-driven gastrointestinal stromal tumours (GISTs). Approved second-line and third-line medical therapies are represented by the TKIs sunitinib and regorafenib, respectively. While imatinib remains the cardinal drug for patients with GISTs, novel therapies are being developed and clinically tested to overcome the mechanisms of resistance after treatments with the approved TKI, or to treat subsets of GISTs driven by rarer molecular events. Here, we review the therapy of GISTs, with a particular focus on the newest drugs in advanced phases of clinical testing that might soon change the current therapeutic algorithm.

scholarly journals Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma

2020 ◽  
pp. 462-470
Author(s):  
Jeronimo Rafael Rodríguez-Cid ◽  
Saul Campos-Gomez ◽  
Vanessa García-Montes ◽  
Manuel Magallanes-Maciel ◽  
Rodrigo Rafael Flores-Mariñelarena ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Toxicity Profile ◽  
Compassionate Use ◽  
Total Study Population ◽  
Free Survival ◽  
Study Population

PURPOSE The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

Lapatinib versus lapatinib plus capecitabine as second-line treatment in HER-2-overexpressing metastatic gastro-esophageal cancer (GC): A randomized phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 112-112
Author(s):  
Sylvie Lorenzen ◽  
Jorge Riera-Knorrenschild ◽  
Georg Martin Haag ◽  
Michael Pohl ◽  
Peter C. Thuss-Patience ◽  
...  
Keyword(s):  
Response Rate ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Her2 Status ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Treatment Groups ◽  
First Line Therapy ◽  
Copy Numbers

112 Background: HER2 amplification is present in a subgroup of gastroesophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-EGFR and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC. Methods: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250 mg per day 1-21 plus capecitabine (CAP) 2000mg/m² on days 1-14 of a 21-day cycle or LAP 1500 mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary endpoint was the objective response rate (ORR) as assessed by the investigator using RECIST 1.1 criteria. We aimed to include 38 pts per arm to show a response rate of >20% in either of the two arms. Results: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines, however, the treatment was intended to be tested as a second-line treatment. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% CI: 1.37 – 34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38 to 61) days in the LAP group and 83 (95% CI: 42 to 86) days in the LAP+CAP group. Other secondary efficacy endpoints (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhea were higher with LAP+CAP (61%; 95% CI: 35 to 83) compared to 26% (95%CI 9 to 51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] vs. 17 [90%]). Conclusions: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. Clinical trial information: NCT01145404.

New frontiers in second-line treatment of Glioblastoma: Re-irradiation in combination with Fotemustine—A single institution experience.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e13511-e13511
Author(s):  
Alicia Marin ◽  
David Büchser ◽  
Margarita Martin ◽  
Mario Lopez ◽  
Laura Fernandez ◽  
...  
Keyword(s):  
Line Treatment ◽  
Second Line ◽  
Single Institution

scholarly journals Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3887
Author(s):  
Valéry Refeno ◽  
Michele Lamuraglia ◽  
Safae Terrisse ◽  
Clément Bonnet ◽  
Clément Dumont ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Saint Louis ◽  
Significant Difference ◽  
Third Line ◽  
Egfr Mutated ◽  
Third Line Treatment

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53–37.6) and the median follow-up duration was 40.83 months (range 11.33–88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

scholarly journals Survival Improvement in the Last 45 Years in Patients with Multiple Myeloma: Real-World Data from a Single Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5573-5573
Author(s):  
Luis Gerardo Rodríguez-Lobato ◽  
Carlos Fernández De Larrea ◽  
Natalia Tovar ◽  
Maria Teresa Cibeira ◽  
Joan Bladé ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Infectious Complications ◽  
Early Mortality ◽  
Line Treatment ◽  
Second Line ◽  
Single Institution ◽  
Group A ◽  
Group B ◽  
Stratified Analysis

Abstract INTRODUCTION: Multiple myeloma (MM) is the second most common blood cancer, with estimated 5-year overall survival (OS) rate of 50%. Survival rates have steadily increased over last decades due to the introduction of high-dose melphalan with autologous stem cell transplantation (ASCT) and newer drugs (thalidomide, lenalidomide and bortezomib). Nevertheless, most studies in MM do not reflect the true real-world population. The aims of the present study were to analyze the survival outcomes, as well as to determine the incidence and causes of early mortality and time to next therapy (TTNT) over time, in patients diagnosed with MM, treated and followed at a single institution. METHODS: We reviewed the clinical records of patients with MM diagnosed at a single institution from January 1970 to December 2015. One thousand one hundred sixty-one patients (591 [50.9%] male; median age at diagnosis 64 years) was the final study population. Median follow-up for alive patients was 5.4 years (range, 0.5-34.4 years). The diagnosis of MM was based on international criteria established during the different periods analyzed. Baseline demographics, clinical and laboratory data, treatment and follow-up were collected. The population was divided into three periods, which included: group A (1970 to 1985), group B (1986 to 1999) and group C (2000 to 2015) (Table 1). The Ethics Committee of the Hospital Clínic of Barcelona approved the study. RESULTS: The median OS (mOS) of all patients was 3.6 years (95% CI: 3.2-3.8). We observed an improvement in mOS during follow-up (Group A: 1.7 years [95% CI: 1.23-2.06]; Group B: 2.92 years [95% CI: 2.44-3.32]; Group C: 5.01 years [95% CI: 4.31-5.52]; p<0.00001). The 5-year OS were 21%, 32% and 50%, respectively (Figure 1A). These findings were maintained in the stratified analysis according to 3 periods by age: < 65 years old (Group A: 1.9 years [95% CI: 1.19-2.54]; Group B: 3.6 years [95% CI: 3.14-4.92]; Group C: 7.5 years [95% CI: 5.64-9.79]; p<0.00001); 65-75 years old (Group A: 1.5 years [95% CI: 0.86-2.26]; Group B: 2.3 years [95% CI: 1.91-2.96]; Group C: 4.3 years [95% CI 3.8-5.25]; p<0.00001); and >75 years old (Group A: 1.1 years [95% CI: 0.12-2.13]; Group B: 1.8 years [95% CI: 1.30-2.74]; Group C: 2.8 years [95% CI: 1.99-3.24]; p<0.001) (Figure 1B to 1D). In the multivariate Cox proportional hazard model, these periods of time retained its independent prognostic value in terms of OS (Group B: HR=0.66; 95% CI 0.55-0.79; p<0.0001; Group C: HR=0.39; 95% CI 0.32-0.47; p<0.00001; compared with Group A). The early mortality rate (first 60 days after diagnosis) was 5.7%; 17.1% in the Group A, 5.7% in Group B, and 2.7% in Group C; p<0.001. The most frequent causes of early mortality were disease-related (46.7%, 63.6% and 66.6%; respectively), and infectious complications (36.7%, 22.7%, and 20.0%; respectively). In terms of time elapse between the start of front-line treatment until the beginning of the subsequent line, the median time to second line treatment in the group A, B and C, were 10.5 months (95% CI: 8.8-14.2), 18.6 months (95% CI: 15.9-21.8), and 26.6 months (95% CI: 23.5-30.7), respectively (p<0.00001) (Figure 1E). In the stratified analysis by age, these positive findings were only observed in the subgroup of patients diagnosed in the period from 2000 to 2015 (<65 years old: 24.6 months [95% CI: 22.1-28.8]; 65-75 years old: 19.1 months [95% CI: 15.6-23.7]; >75 years old: 15 months [95% CI: 9.4-18.5]; p<0.001) (Figure 1F). Regarding subsequent treatment lines (3rd and 4th), we did not observe statistically significant differences in TTNT neither by age nor by treatment periods. CONCLUSIONS: This study shows that the survival outcome have significantly improved over the last decades in all age groups, including the elderly, due to ASCT and novel drugs. The incidence of early mortality is low, being the most frequent MM progression and infectious complications. Finally, the time to second line treatment has increased, specifically during the period from 2000 to 2015, with no differences in subsequent lines. Disclosures Bladé: Janssen: Honoraria. Rosinol:Janssen, Celgene, Amgen, Takeda: Honoraria.

scholarly journals VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature

2021 ◽  
Vol 11 ◽  
Author(s):  
Aikaterini Liapi ◽  
Patrice Mathevet ◽  
Fernanda G. Herrera ◽  
Delfyne Hastir ◽  
Apostolos Sarivalasis
Keyword(s):  
Kinase Inhibitor ◽  
Bone Biopsy ◽  
Single Agent ◽  
Bone Lesion ◽  
Mtor Inhibitors ◽  
Epithelioid Cell ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Progression ◽  
Tsc1 Gene

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.

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