scholarly journals Effect of trifluridine/tipiracil in patients treated in RECOURSE by prognostic factors at baseline: an exploratory analysis

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000752
Author(s):  
Josep Tabernero ◽  
Guillem Argiles ◽  
Alberto F Sobrero ◽  
Christophe Borg ◽  
Atsushi Ohtsu ◽  
...  

BackgroundThe choice of treatment in patients with metastatic colorectal cancer (mCRC) is generally influenced by tumour and patient characteristics, treatment efficacy and tolerability, and quality of life. Better patient selection might lead to improved outcomes.MethodsThis post hoc exploratory analysis examined the effect of prognostic factors on outcomes in the Randomized, Double-blind, Phase 3 Study of trifluridine tipiracil (FTD/TPI) plus Best Supportive Care (BSC) versus Placebo plus BSC in Patients with mCRC Refractory to Standard Chemotherapies (RECOURSE) trial. Patients were redivided by prognosis into two subgroups: those with <3 metastatic sites at randomisation (low tumour burden) and ≥18 months from diagnosis of metastatic disease to randomisation (indolent disease) were included in the good prognostic characteristics (GPC) subgroup; the remaining patients were considered to have poor prognostic characteristics (PPC).ResultsGPC patients (n=386) had improved outcome versus PPC patients (n=414) in both the trifluridine/tipiracil and placebo arms. GPC patients receiving trifluridine/tipiracil (n=261) had an improved median overall survival (9.3 vs 5.3 months; HR (95% CI) 0.46 (0.37 to 0.57), p<0.0001) and progression-free survival (3.3 vs 1.9 months; HR (95% CI) 0.56 (0.46 to 0.67), p<0.0001) than PPC patients receiving trifluridine/tipiracil (n=273). Improvements in survival were irrespective of age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), KRAS mutational status, and site of metastases at randomisation. In the trifluridine/tipiracil arm, time to deterioration of ECOG PS to ≥2 and proportion of patients with PS=0–1 discontinuing treatment were longer for GPC than for PPC patients (7.8 vs 4.2 months and 89.1% vs 78.4%, respectively).ConclusionLow tumour burden and indolent disease were factors of good prognosis in late-line mCRC, with patients experiencing longer progression-free survival and greater overall survival.

2020 ◽  
pp. 107815522092408 ◽  
Author(s):  
Deniz Tataroglu Ozyukseler ◽  
Mustafa Basak ◽  
Seval Ay ◽  
Aygül Koseoglu ◽  
Serdar Arıcı ◽  
...  

Background Ado-trastuzumab emtansine is an antibody-drug conjugate that combines the cytotoxic activity of emtansine with human epidermal growth factor receptor 2-targeted antitumor features of trastuzumab. Objective We conducted a study of metastatic breast cancer patients treated with trastuzumab emtansine. By evaluating progression-free survival, overall survival, and response rates, we aimed to find prognostic factors of trastuzumab emtansine treatment. Methods Our study is a single-center, retrospective, observational study. We have clinical data from 78 patients treated with trastuzumab emtansine for metastatic breast cancer, from May 2016 through May 2019, at Kartal Dr Lutfi Kirdar Education and Research Hospital, Medical Oncology Department. Our objective is to assess the survival and response rates in trastuzumab emtansine-treated individuals and the factors associated with survival. The factors we analyzed were cancer antigen 15-3 sensitivity, Eastern Cooperative Oncology Group-Performance Status, presence or absence of visceral metastases, presence or absence of cranial metastases, and treatment-associated thrombocytopenia. Results Among 78 patients, median progression-free survival was 7.8 months, and overall survival was 21.1 months. Twenty of the patients had an objective tumor response. The results showed that trastuzumab emtansine was tolerable with a manageable safety profile and consistent with the results of the previous literature. Mostly seen adverse events were anemia, thrombocytopenia, fatigue, and increased levels of alkaline phosphatase. Patients with Eastern Cooperative Oncology Group-Performance Status = 2 had worse progression-free survival and overall survival compared to ones with Eastern Cooperative Oncology Group-Performance Status < 2; progression-free survival and overall survival are worse in cancer antigen 15-3-sensitive breast cancer patients. According to our findings, treatment-associated thrombocytopenia was a significant prognostic factor for survival. Patients with thrombocytopenia had 12 months progression-free survival, whereas patients without thrombocytopenia had only 4.1 months progression-free survival. In like manner, overall survival was much better in the thrombocytopenia-experienced patients as 29.5 versus 11.8 months. Conclusions Trastuzumab emtansine prolongs progression-free survival and overall survival with a manageable safety profile. Thrombocytopenia, Eastern Cooperative Oncology Group-Performance Status, and cancer antigen 15-3 are correlated with progression-free survival and/or overall survival.


2020 ◽  
pp. 107815522092068
Author(s):  
Ozkan Alan ◽  
Tugba Akin Telli ◽  
Tugba Basoglu Tuylu ◽  
Rukiye Arikan ◽  
Nazım Can Demircan ◽  
...  

Purpose Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. Methods Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. Results At the time of diagnosis, the median age was 48 (17–77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1–68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). Conclusion Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.


2010 ◽  
Vol 28 (18) ◽  
pp. 2947-2951 ◽  
Author(s):  
Weijing Sun ◽  
Mark Powell ◽  
Peter J. O'Dwyer ◽  
Paul Catalano ◽  
Rafat H. Ansari ◽  
...  

Purpose The combination of sorafenib with chemotherapy is well-tolerated and is associated with encouraging response rates in several malignances. Both docetaxel and cisplatin are active in gastric cancer. A phase II study was conducted to determine the efficacy and toxicity of combined sorafenib, docetaxel, and cisplatin in patients with metastatic or advanced adenocarcinoma of stomach or gastroesophageal junction (GEJ). Patients and Methods Forty-four chemotherapy-naïve patients with Eastern Cooperative Oncology Group performance status 0 or 1, of whom 80% had metastatic disease and two thirds had poorly differentiated gastric or GEJ adenocarcinoma, were enrolled. The treatment regimen was sorafenib 400 mg orally twice a day for 21 days, docetaxel 75 mg/m2 intravenously on day 1, and cisplatin 75 mg/m2 intravenously on day 1, repeated every 21 days. The primary end point was response rate to the combination. Toxicity, overall survival, and progression-free survival were assessed as secondary end points. Results Eighteen of the 44 eligible and treated patients showed partial responses (41%; 90% CI, 28% to 54%). The median progression-free survival was 5.8 months (90% CI, 5.4 to 7.4 months). The median overall survival was 13.6 months (90% CI, 8.6 to 16.1 month). The major toxicity of this regimen was neutropenia, which reached grade 3 to 4 in 64% of patients. One patient experienced hemorrhage at the tumor site. Conclusion The combination of sorafenib, docetaxel, and cisplatin has an encouraging efficacy profile with tolerable toxicity. Additional studies of sorafenib with chemotherapy are warranted in gastric cancer.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5111-5111
Author(s):  
Jeongseok Kim ◽  
Dok Hyun Yoon ◽  
Ji Hyun Park ◽  
Il Young Jang ◽  
Shin Kim ◽  
...  

Abstract Abstract 5111 Purpose We aimed to evaluate the clinicopathologic characteristics and clinical outcomes in patients with testicular non-Hodgkin lymphoma. Material and Methods We reviewed the medical records of 24 patients with testicular non-Hodgkin lymphoma diagnosed at the Asan Medical Center between November, 2000 and June, 2012. Results Median age of the patients was 52 years (23–79 years). Histopathologic subtypes were as follows: DLBCL (n=18, 75%), Burkitt's lymphoma (n=2, 8. 3%), extranodal natural killer/T-cell lymphoma (NKTCL) (n=2, 8. 3%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n=1, 4. 2%) and T-cell lymphoblastic lymphoma (T-LBL) (n=1, 4. 2%). Ten patients (41. 7%) were in stage I, 1 patient (4. 2%) in stage II, and the other 13 patients (54. 2%) were in stage IV. Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 1 in 22 patients (87. 5%) and >1 in 5 patients (20. 8%). Serum LDH levels were elevated in 14 patients (58. 3%). International Prognostic index (IPI) score was low (0–1) in 6 patients (25%), low-intermediate (2) in 8 patients (33. 3%), high-intermediate (3) in 7 patients (29. 2%), high (4–5) in 3 patients (12. 5%). B-symptoms were present in 4 patients (16. 7%). Bilateral testicular involvement was observed in 5 patients (20. 8%). Fifteen patients (62. 5%) underwent orchiectomy as an initial therapeutic and diagnostic procedure. All the patients underwent chemotherapy: R-CHOP (n=16, 66. 6%), CHOP (n=2, 8. 3%), and other regimens (n=6, 25%). None received intrathecal prophylaxis just except a T-LBL patient. Prophylactic radiotherapy to contralateral testis was given in 12 patients (50%). Twenty-one patients (87. 5%) achieved complete response. At a median follow-up duration of 22 months (1–139 months), 2 patients (8. 3%) showed disease progression and 7 patients (29. 2%) experienced disease recurrence; in the central nervous system (n=2, 8. 3%), regional lymph nodes (n=3, 12. 5%), bone marrow (n=1, 4. 2%), nasopharynx (n=1), skin (n=1), and testicular bed (n=1). Five patients (20. 8%) died of sepsis (n=3, 12. 5%) or progression of disease (n=2, 8. 3%). Median progression free survival and overall survival were 20 months (1–139 months) and 22 months (1–139 months), respectively. ECOG PS >1 (p=0. 015) and bilateral testicular involvement (p=0. 000) were associated with a significantly short progression free survival (PFS). ECOG PS >1 (p=0. 001), high-intermediate or high risk of IPI (p=0. 010), presence of B symptoms (p=0. 035), and bilateral testicular involvement (p=0. 001) were associated with a significantly short overall survival. Conclusions Testicular lymphoma is a rare but aggressive extranodal lymphoma. High ECOG PS, high IPI, B symptom, and bilateral testicular involvement were associated with poor prognosis. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.


2019 ◽  
Vol 29 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Cem Onal ◽  
Berna Akkus Yildirim ◽  
Sezin Yuce Sari ◽  
Guler Yavas ◽  
Melis Gultekin ◽  
...  

ObjectiveTo analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis.MethodsData from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed.ResultsThe 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001 and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02 and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival.ConclusionWe demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.


2020 ◽  
Vol 28 (3) ◽  
pp. 230949902097450
Author(s):  
Feryel Letaief ◽  
Salim Khrouf ◽  
Yosra Yahiaoui ◽  
Adel Hamdi ◽  
Azza Gabsi ◽  
...  

Background: Osteosarcoma is the most frequent bone cancer occurring in children and adolescents aged 10–20 years. Several prognostic factors have been identified by studies done at western centers. The aim of our study was to identify the prognostic factors in Tunisian patients in order to improve their management. Methods: We reviewed the data of localized limb osteosarcoma patients treated in Salah Azaïz Institute from January 1980 to December 2018. Patient’s treatment and survival variables were assessed. Patients received a neoadjuvant chemotherapy and underwent surgery in an expert center. They received afterward an adjuvant chemotherapy depending on the tumor necrosis assessed by Huvos. Results: Eighty-five patients were enrolled. Mean duration of follow-up was 30 months (range 1–297 months). Males were 1.6 times more frequent, median age was 17 (from 1 to 62 years). Conventional osteoblastic osteosarcoma was the most frequent histological subtype (77%). Median tumor size was 10 cm. Femoral location was the most frequent (60%). The overall average history of symptoms was 103 days (4 to 423 days). The 5-year overall-survival was 38% and the event free survival 32%. Tumor site, lactate dehydrogenase levels, high methotrexate levels at 24 h, clinical evaluation of the tumor perimeter, surgery type and delay of relapse were found to affect overall survival. Tumor site, Lactate dehydrogenase levels and clinical evaluation of the tumor perimeter affected the progression free survival. Conclusion: Demographic characteristics of Tunisian patients are mainly the same than worldwide. Femoral site, normal level of lactate dehydrogenase, a clinical response during neoadjuvant treatment, an R0 surgery, a delay of relapse over 2 years and Median H24 Methotrexate level superior to 4.4 µmol/l were associated with a better prognosis in our study.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P &lt;0.00001), labeling index (0.25; &lt;0.0001), creatinine (0.23; &lt;0.0001), soluble IL6 receptor (0.3; &lt;0.0001), BM plasma cell percentage (0.16; &lt;0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P &lt; 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P &lt; 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P &lt; 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 142-142
Author(s):  
Montserrat Mangas ◽  
Alberto Carmona Bayonas ◽  
Maria Luisa Sanchez Lorenzo ◽  
Avinash Ramchandani ◽  
Teresa Garcia ◽  
...  

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]


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