scholarly journals Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the Phase III MabCute study

Haematologica ◽  
2021 ◽  
Author(s):  
Simon Rule ◽  
Wolney Gois Barreto ◽  
Javier Briones ◽  
Angelo M. Carella ◽  
Olivier Casasnovas ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Log Rank Test ◽  
Chemotherapy Induction

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers long-term progression-free survival (PFS) benefit in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years’ initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed PFS in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 PFS events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log rank test; hazard ratio 0.76 [95% confidence interval: 0.37–1.53]). Median PFS was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non-Hodgkin lymphoma.

scholarly journals Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma

2019 ◽  
Vol 185 (4) ◽  
pp. 670-678 ◽  
Author(s):  
Tamer Khashab ◽  
Fredrick Hagemeister ◽  
Jorge E. Romaguera ◽  
Michelle A. Fanale ◽  
Barbara Pro ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Non Hodgkin Lymphoma

scholarly journals Role of Bevacizumab in High-grade Meningiomas

2021 ◽  
Author(s):  
Xuexue Bai ◽  
xiangyu wang ◽  
Yiyao Cao
Keyword(s):  
Progression Free Survival ◽  
Rank Test ◽  
High Grade ◽  
Chi Square ◽  
Free Survival ◽  
Log Rank Test ◽  
Peritumoral Brain Edema ◽  
Chi Square Test

Abstract Background: To explore the role of bevacizumab (BV) in High-grade Meningiomas (HGMs) undergoing surgical treatment.Methods: Review the clinical data of 139 patients with HGMs and divide them into BV group and non- BV group according to whether they receive BV treatment. Then we compared the progression-free survival (PFS) and overall survival (OS) of the two groups.Results: The Chi-square test showed significant differences between the BV group and the non-BV group in terms of 12-month PFS (PFS-12), 36-month PFS (PFS-36), median PFS (M-PFS), 12-month OS (OS-12), 36-month OS (OS-36), and median OS (M-OS). However, there was no statistical difference between the BV group and the non-BV group in terms of 6-month PFS (PFS-6), 60-month PFS (PFS-60), and 60-month OS (OS-60). The log-rank test indicated significant differences in PFS and OS between the BV group and the non-BV group.Conclusion: The role of BV in patients with HGMs is to relieve the symptoms of peritumoral brain edema (PTBE) and prolong PFS and OS. However, whether increasing the dose of BV after surgery can improve the long-term PFS and OS of patients with HGMs needs further research.

scholarly journals Phase III Trial of Carboplatin and Paclitaxel With or Without Sorafenib in Metastatic Melanoma

2013 ◽  
Vol 31 (3) ◽  
pp. 373-379 ◽  
Author(s):  
Keith T. Flaherty ◽  
Sandra J. Lee ◽  
Fengmin Zhao ◽  
Lynn M. Schuchter ◽  
Lawrence Flaherty ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
End Points ◽  
Free Survival ◽  
Log Rank Test ◽  
The Difference

Purpose The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma. Patients and Methods In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m2 intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity. Results In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference. Conclusion Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma.

scholarly journals Rituximab Maintenance Treatment for a Maximum of 5 Years in Follicular Lymphoma: Final Results of the Randomized Phase III Trial SAKK 35/03

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1601-1601 ◽  
Author(s):  
Christian Taverna ◽  
Giovanni Martinelli ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Iii ◽  
Rank Test ◽  
Short Term ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Log Rank Test ◽  
Term Maintenance

Abstract Background: Follicular lymphoma is usually a disase with a prolonged course and a chemotherapy-free regimen might be a favourable treatment strategy. SAKK 35/03 investigated two different durations of rituximab maintenance (5 years vs. 6 months) in patients with follicular lymphoma after induction with 4 weekly doses of rituximab monotherapy. With a median follow-up of 6.4 years we were not able to show a benefit with long-term rituximab maintenance up to five years in event-free survival (EFS) or overall survival (OS ). Here we report the final results with a median follow-up of 10 years. Methods: 270 patients (median age 57 years: range 25-82) with untreated, relapsed, stable or chemotherapy resistant follicular lymphoma were treated with 4 doses of rituximab monotherapy in weekly intervals (375 mg/m²). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of five years or until disease progression or unacceptable toxicity). The primary endpoint was EFS . Progression-free survival (PFS), OS, and toxicity were secondary endpoints. Comparisons between the two treatment arms were performed using the log-rank test for survival endpoints. Results: 165 patients were randomly assigned to short-term (n=82) or long-term (n=83) maintenance. At a median follow-up period of 10 years, the median EFS is 3.4 years (95% CI 2.1-5.5) in the short-term arm and 5.3 years (95% CI 3.5-7.5) in the long-term arm. Using the pre-specified log-rank test this difference is statistically not significant (p=0.39 ). There is no significant difference in PFS and OS. Median OS in the short-term arm is 11.0 years (95% CI 11.0, NA ) and not reached in the long-term arm (p=0.80). The incidence of subsequent cancers increased in both arms over time, nine patients developed a subsequent cancer in the short-term maintenance arm and 10 in the long-term maintenance arm. There was no major additional toxicity with longer follow-up. Conclusions : Even with a long follow-up of 10 years we were not able to show a significant benefit of long-term compared to short-term rituximab maintenance in EFS, PFS and OS. Treatment strategies and study designs need to take these results into consideration in order to guarantee optimal medical and scientific results. Disclosures Zucca: Celltrion: Consultancy; AstraZeneca: Consultancy. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Glioblastoma and Increased Survival with Longer Chemotherapy Duration

2019 ◽  
Vol 12 (3) ◽  
pp. 65-69 ◽  
Author(s):  
Dory Abou Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  
Keyword(s):  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Optimal Duration ◽  
Multicenter Prospective Study ◽  
One Year

Introduction The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment. Methods This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year. Results Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ2 (1, N = 56) = 19.2, p < 0.0001). Conclusions There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to dentify optimal duration of TMZ therapy.

Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit

2004 ◽  
Vol 22 (21) ◽  
pp. 4272-4281 ◽  
Author(s):  
Hans Herbert Steiner ◽  
Matteo Mario Bonsanto ◽  
Philipp Beckhove ◽  
Michael Brysch ◽  
Karsten Geletneky ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cell ◽  
Progression Free Survival ◽  
Delayed Type Hypersensitivity ◽  
Rank Test ◽  
Autologous Tumor ◽  
Free Survival ◽  
Log Rank Test ◽  
Long Term Survivors

Purpose Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. Patients and Methods In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. Results Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (≥ 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8+ tumor-infiltrating T-lymphocytes in secondary tumors. Conclusion Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.

scholarly journals Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma

2017 ◽  
Vol 13 (01) ◽  
pp. 1
Author(s):  
Antonio M Grimaldi ◽  
Ester Simeone ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Paolo A Ascierto ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Combined Therapy ◽  
Acquired Resistance ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Mek Inhibition ◽  
Braf Mutant

Acquired resistance is the most common cause of BRAF inhibitor monotherapy treatment failure, with the majority of patients experiencing disease progression with a median progression-free survival of 6-8 months. As such, there has been considerable focus on combined therapy with dual BRAF and MEK inhibition as a means to improve outcomes compared with monotherapy. In the COMBI-d and COMBI-v trials, combined dabrafenib and trametinib was associated with significant improvements in outcomes compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF-mutant metastatic melanoma. The combination of vemurafenib and cobimetinib has also been investigated. In the phase III CoBRIM study in patients with unresectable stage III-IV BRAF-mutant melanoma, treatment with vemurafenib and cobimetinib resulted in significantly longer progression-free survival and overall survival (OS) compared with vemurafenib alone. One-year OS was 74.5% in the vemurafenib and cobimetinib group and 63.8% in the vemurafenib group, while 2-year OS rates were 48.3% and 38.0%, respectively. The combination was also well tolerated, with a lower incidence of cutaneous squamous-cell carcinoma and keratoacanthoma compared with monotherapy. Dual inhibition of both MEK and BRAF appears to provide a more potent and durable anti-tumour effect than BRAF monotherapy, helping to prevent acquired resistance as well as decreasing adverse events related to BRAF inhibitor-induced activation of the MAPK-pathway. Combined BRAF and MEK inhibition is the standard of care in patients with advanced BRAF-mutant melanoma.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

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