Zervixkarzinom: Immuntherapie hält Einzug in die Erstlinie

2021 ◽  
pp. 1-2
Author(s):  
Linn Wölber
Keyword(s):  
Phase Iii ◽  
Systemische Chemotherapie ◽  
Intention To Treat ◽  
Kurative Behandlung ◽  
Treat Population

Die Keynote-826 Studie untersucht die Wirksamkeit von Pembrolizumab bei metastasiertem, rezidiviertem oder persistenten Gebärmutterhalskrebs, der unter Chemotherapie progredient ist. Eingeschlossen wurden Patientinnen mit Plattenepithelkarzinom, adenosquamösem Karzinom oder Adenokarzinom des Gebärmutterhalses, die bisher keine systemische Chemotherapie für die metastasierte oder rezidvierte Situation erhalten hatten und bei denen eine kurative Behandlung (wie Operation und/oder Bestrahlung) nicht mehr in Frage kam. In der doppelblinden Phase-III-Studie wurden Patientinnen im Verhältnis 1:1 randomisiert. Untersucht wurde der Nutzen der der Zugabe von Pembrolizumab zur Chemotherapie mit oder ohne Bevacizumab. Primäre Endpunkte waren das progressionsfreie Überleben (PFS) und das Gesamtüberleben (OS). Bei Ergänzung mit Pembrolizumab betrug das mediane progressionsfreie Überleben von 548 Patientinnen (kombinierter PD-L1-Score ≥1) 10,4 Monate, in der Placebo-Gruppe 8,2 Monate. In der Intention-to-Treat-Population (617 Patientinnen) lag das progressionsfreie Überleben bei 10,4 Monate bzw. 8,2 Monate. Bei 317 Patienten mit einem kombinierten positiven PD-L1-Score von 10 oder mehr betrug das progressionsfreie Überleben 10,4 Monate bzw. 8,1 Monate. In der Pembrolizumab-Gruppe lag das Gesamtüberleben nach 24 Monaten bei 53,0 % und 41,7 % in der Placebo-Gruppe, bzw. 50,4 % und 40,4 % sowie 54,4 % und 44,6 %. Demzufolge zeigten die Patientinnen unter Pembrolizumab ein signifikant längeres progressionsfreies und Gesamtüberleben als unter Placebo.

Once-Daily Oral Rivaroxaban Compared with Subcutaneous Enoxaparin Every 12 Hours for Thromboprophylaxis after Total Knee Replacement: RECORD4

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 35-35 ◽  
Author(s):  
Alexander GG Turpie ◽  
Kenneth A. Bauer ◽  
Bruce Davidson ◽  
Michael Gent ◽  
Louis Kwong ◽  
...  
Keyword(s):  
Total Knee Replacement ◽  
Knee Replacement ◽  
Major Bleeding ◽  
Phase Iii ◽  
Primary Efficacy ◽  
Once Daily ◽  
Intention To Treat ◽  
Protocol Population ◽  
Total Knee ◽  
Treat Population

Abstract Rivaroxaban is an oral, direct Factor Xa inhibitor that has been evaluated in the RECORD phase III clinical trial program for the prevention of venous thromboembolism (VTE) in major orthopaedic surgery. RECORD3 (Lassen M, et al. N Engl J Med2008;358:2776–2786) showed that oral rivaroxaban 10 mg once daily (od) given post-operatively significantly reduced VTE after total knee replacement (TKR), compared with subcutaneous (s.c.) enoxaparin 40 mg od initiated pre-operatively, with similar rates of bleeding. RECORD4 was designed to determine the efficacy and safety of rivaroxaban compared with enoxaparin 30 mg administered twice daily after TKR. Patients (N=3,148) were randomized to receive either oral rivaroxaban 10 mg od (initiated 6–8 hours after surgery) or s.c. enoxaparin 30 mg every 12 hours (initiated 12 to 24 hours after surgery) for 10 to 14 days. Patients underwent mandatory, bilateral venography between day 11 and day 15. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality up to day 17. The primary efficacy analysis was a test for non-inferiority in the per-protocol population (n=1,702), followed by a test for superiority in the modified intention-to-treat population (n=1,924) (if non-inferiority was established in the per-protocol population). The main secondary efficacy endpoint was major VTE: the composite of proximal DVT, non-fatal PE, and VTE-related death. Treatment-emergent major bleeding observed no later than two days after the last intake of study was the main safety endpoint. The results are shown in the table. Rivaroxaban significantly reduced the incidence of the primary efficacy outcome compared with enoxaparin (6.9% vs 10.1%, respectively; p=0.012; relative risk reduction 31%). Rivaroxaban was non-inferior to enoxaparin for the prevention of major VTE in the per-protocol population (p<0.001). The observed incidences of major VTE and symptomatic VTE in those receiving rivaroxaban or enoxaparin were 1.2% vs 2.0% (p=0.124), and 0.7% vs 1.2% (p=0.187), respectively, and the rates of major bleeding were 0.7% vs 0.3% (p=0.110) respectively, and major and clinically relevant non-major bleeding 3.0% vs 2.3% (p=0.179) in the rivaroxaban and enoxaparin treated groups, respectively. The data demonstrate that rivaroxaban has superior efficacy to enoxaparin 30 mg administered every 12 hours for the prevention of VTE after TKR, without significantly increasing the risk of bleeding. Endpoint Rivaroxaban10 mg od % (n/N) Enoxaparin30 mg q12h % (n/N) p-value for differenced aModified intention-to-treat population bModified intention-to-treat population valid for major VTE analysis cSafety population dCalculated for the absolute risk difference DVT, non-fatal PE, and all-cause mortalitya 6.9% (67/965) 10.1% (97/959) 0.012 Major VTEb 1.2% (13/1,122) 2.0% (22/1,112) 0.124 Symptomatic VTEc 0.7% (11/1,526) 1.2% (18/1,508) 0.187 Major bleedingc 0.7% (10/1,526) 0.3% (4/1,508) 0.110 Any non-major bleedingc 10.2% (155/1,526) 9.2% (138/1,508) – Major and clinically relevant non-major bleedingc 3.0% (46/1526) 2.3% (34/1,508) 0.179

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

scholarly journals Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

2018 ◽  
Vol 24 (14) ◽  
pp. 1862-1870 ◽  
Author(s):  
Edward J Fox ◽  
Clyde Markowitz ◽  
Angela Applebee ◽  
Xavier Montalban ◽  
Jerry S Wolinsky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Upper Extremity ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Intention To Treat ◽  
Disability Status ◽  
Upper Extremity Impairment ◽  
Post Hoc

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS). Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO. Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT. Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses. Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.

Post Hoc Economic Analysis of Temozolomide Versus Dacarbazine in the Treatment of Advanced Metastatic Melanoma

2000 ◽  
Vol 18 (7) ◽  
pp. 1474-1480 ◽  
Author(s):  
Bruce E. Hillner ◽  
Sanjiv Agarwala ◽  
Mark R. Middleton
Keyword(s):  
Metastatic Melanoma ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Survival Times ◽  
Economic Implications ◽  
Intention To Treat ◽  
Hazard Ratios ◽  
The Mean ◽  
Post Hoc

PURPOSE: To determine the potential economic implications resulting from oral temozolomide (TEM) compared with intravenous (IV) dacarbazine (DTIC) for metastatic melanoma. PATIENTS AND METHODS: We performed a cost-effectiveness (CE) analysis using hazard ratios (HRs) from the phase III (Schering I95–018) trial comparing TEM 200 mg/m2/d orally for 5 days every 28 days with DTIC 250 mg/m2/d IV for 5 days every 21 days. Sensitivity analyses assessed a range of TEM’s efficacy and costs, direct nonmedical costs, and the DTIC schedule. RESULTS: The trial found an overall survival trend favoring TEM; median survival times of patients treated with DTIC and TEM were 6.4 and 7.7 months, respectively (HR = 1.18; 95% confidence interval [CI], 0.92 to 1.52; intention to treat, P = .20). The mean increase in survival of TEM over DTIC was 1.1 months. The projected average costs per patient were greater with TEM than DTIC ($6,902 v $3,697, respectively). The incremental CE ratio using TEM was $36,990 per life-year or $101 per day of life gained. The CE ratio’s 95% CI ranged from −$65,180 (DTIC is more effective) to $18,670 per year of life gained. The CE ratios decreased 50% if direct nonmedical costs were included and increased 50% if DTIC’s efficacy was unchanged if given as a single daily dosage. Sixty percent of simulations found TEM with a CE threshold of less than $50,000 per life-year gained. CONCLUSION: Although the base-case efficacy of TEM compared with DTIC was not statistically significant, its associated incremental CE would be comparable with many interventions. TEM for metastatic melanoma illustrates the tension confronting providers choosing between similar agents that markedly differ in convenience and costs.

Characteristics and Outcome Of 66 Patients With Extramedullary Plasmacytomas (EMPs) Included In a Phase III Pethema/GEM Study Of Induction Therapy Prior Autologous Stem Cell Transplantation (ASCT) In Multiple Myeloma (MM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3188-3188
Author(s):  
Laura Rosiñol ◽  
Raquel Jiménez-Segura ◽  
Ana Isabel Teruel ◽  
Javier De La Rubia ◽  
Maria Victoria Mateos ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Statistical Significance ◽  
Phase Iii ◽  
Advisory Committees ◽  
Intention To Treat ◽  
Extramedullary Disease ◽  
The Difference ◽  
Extramedullary Plasmacytomas

Abstract Introduction In April 2006, the Spanish Myeloma Group (PETHEMA/GEM) initiated a randomized phase III trial (GEM05menos65) comparing induction with thalidomide/dexamethasone (TD) vs. bortezomiv/thalidomide/dexamethasone (VTD) vs. VBMCP/VBAD/Bortezomib (VBMCP/VBAD/B) in patients 65 years-old or younger with newly diagnosed symptomatic MM followed by ASCT with MEL-200 and maintenance therapy with interferon vs, thalidomide alone or bortezomib/thalidomide. The results of the overall series has been previously published. However, the efficacy of novel agents in patients with extramedullary disease is not well stablished. Primary end points to describe the characteristics and outcome of patients with EMPs homogeneously treated in the GEM05menos65 trial. Patients and Methods TD consisted of thalidomide 200 mg daily (escalating doses in the first cycle) and dexamethasone 40 mg on days 1-4 and 9-12 at 4-week intervals for 6 cycles. The VTD regimen was identical to TD plus i.v. bortezomib 1.3 mg/m2 on days 1,4,8,11 of each cycle. Combination chemotherapy plus bortezomib consisted of 4 cycles of VBMCP/VBAD on an alternating basis followed by 2 cycles of i.v. bortezomib (1.3 mg/m2 on days 1,4,8, and 11 every 3 weeks). The duration of the induction therapy was 24 weeks in all arms. From April 6, 2006 to August 5, 2009 the 390 planned patients entered the study. 66 patients (17%) had extramedullary plasmacytomas (median age: 54 years, M: 33, F: 33). The isotype was IgG: 41, IgA 11, Bence-Jones: 10, IgD:4; kappa:41, lambda: 25.The stage according to the ISS was I in 27 patients, II in 26 and III in 13 patients. The location of the EMPs was soft-tissue masses arising from lytic lesions in 60 patients, testicular mass with no contact with bone in 1 case and was not specified in 6 cases. Nine patients had multiple extraosseous plasmacytomas. 17 patients received induction therapy with VBMCP/VBAD/B, 23 with TD and 26 with VTD. Results Cytogenetic information was available in 51 out of the 66 cases with EMPs and 12 of them (23%) showed high-risk cytogenetics. There were no differences in the incidence of high-risk cytogenetics (t(4;14), t(14;16) and del 17p) in patients with and without EMPs (23% vs 21%). The incidence of t(4;14) in patients with and without EMP was 16% vs 23%, respectively. The incidence of del 17p was 10% and 6% in patients with and without EMPs.The IFE negative CR rate was significantly higher with VTD as compared to TD (42% vs 13%, p=0.02) while there was no significantly differences among VTD and VBMCP/VBAD/B (42% vs 29%, p=NS). Patients with EMP had a significantly higher rate of PD during induction therapy as compared to patients without EMPs (24% vs 11%, p=0.01). This higher rate of PD in patients with EMP was observed in the 3 induction arms (VBMCP/VBAD/B 24% vs 9%, TD 40% vs 19%, VTD 12% vs 6%). 43 patients received ASCT as part of the treatment design. On an intention to treat basis, the pos-ASCT CR rate was higher with VTD arm compared to TD (50% vs 22%, p=0.07) but not significantly different from VBMCP/VBAD/B (50% vs 41%, p=0.7). After a median follow-up of 46 months, there was no significant differences in PFS between patients with or without EMP (26.9 vs 39.9 months, p=0.47). Although the difference did not reach statistical significance, there was a trend towards a shorter PFS for patients with EMPs with high-risk cytogenetics (median 12.1 vs. 28.3 months, p=0.13). In patients with EMPS, the PFS was not reached in the VTD arm versus 26.9 months with VBMCP/VAB/B and 22.8 moths with TD. The OS was significantly shorter in patients with EMPs as compared to patients without EMPs (median 69.9 months vs not reached, p=0.02) Conclusion 1) In the present study the frequency of EMPs was 17%, 2) the incidence of high-risk cytogenetics in patients with EMPs was similar to that observed in patients with no extramedullary disease, 3) patients with EMPs had a higher rate of progressive disease irrespective of the induction arm as compared to patients without EMPs, being VTD the best treatment option, 4) finally, the OS was significantly shorter in patients with EMPs. Disclosures: Rosiñol: Janssen: Honoraria; Celgene: Honoraria. De La Rubia:Janssen: Honoraria; Celgene: Honoraria. Mateos:Jansen: Honoraria; Celgene: Honoraria. Tomas:MedImmune: Research Funding. Gutiérrez:Jansen: Honoraria; Celgene: Honoraria. San Miguel:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. Blade:Janssen: Honoraria; Celgene: Honoraria.

Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 816-816 ◽  
Author(s):  
Ralf Ulrich Trappe ◽  
Daan Dierickx ◽  
Heiner Zimmermann ◽  
Franck Morschhauser ◽  
Peter Mollee ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Ii Trial ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Advisory Committees ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Treat Population

Abstract Background: The PTLD-1 trial has demonstrated the efficacy and safety of 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF in CD20-positive PTLD after solid organ transplantation. Median overall survival (OS) was 6.6 years, a clear improvement over the preceding rituximab monotherapy trials (2.4 years). However, response to rituximab induction predicted OS after completion of therapy. Based on the hypothesis that rituximab consolidation might be sufficient treatment for patients already in a complete response (CR) after rituximab induction, trial treatment was changed in 2007 through a protocol amendment introducing risk-stratified sequential treatment (RSST): rituximab consolidation for patients in CR after rituximab induction and R-CHOP-21 consolidation for all others. Methods: In this international, multicenter phase II trial (PTLD-1, 3rd amendment; NCT00590447), treatment-naïve adult solid organ transplant recipients diagnosed with CD20-positive PTLD were treated with rituximab (375 mg/m2 IV) on days 1, 8, 15 and 22. After restaging, patients in CR continued with four three-weekly courses of rituximab monotherapy while all others received 4 cycles of R-CHOP-21 + G-CSF. In case of disease progression during rituximab monotherapy R-CHOP was commenced immediately. The primary endpoint was treatment efficacy measured as response rates and response duration. Analysis was by intention to treat. This is the final analysis of 152 patients treated with RSST from 2007 to 2014 at centers in Germany (72), Belgium (36), France (24), Australia (7), Poland (7) and Italy (6) with a median follow-up of 4.5 years. The 70 patients treated with rituximab followed by CHOP-21 in the original PTLD-1 trial (median follow-up 5.1 years) served as a control population. Inclusion criteria and follow-up schedule were identical; there were no significant differences in the transplant- and lymphoma-related baseline factors listed below. Results: 115/152 patients were male. 69/152 were kidney, 40 liver, 18 lung, 15 heart, 5 heart/kidney, 3 kidney/pancreas and 2 heart/lung transplant recipients. Median age at diagnosis was 56 years. PTLD was late (> 1 year after transplantation) in 120/152 (79%) of patients. 67/145 (46%) PTLD were EBV-associated. 130/152 patients had monomorphic, 20 polymorphic and 2 early lesion PTLD. The overall response rate (ORR) was 111/126 (88%, CR: 88/126 [70%]). Median duration of remission (DR) was not reached; the 3-year Kaplan-Meier estimate was 82% (compared to 71% in PTLD-1). In the intention-to-treat population (152 patients), the median time to progression (TTP) was not reached either. The 3-year Kaplan-Meier estimate was 78% (69% in PTLD-1). Median OS by intention-to-treat was 6.6 years (95% CI 5.5 - 7.6) with a 3-year estimate of 70% in comparison to 61% in PTLD-1. There was no significant difference in ORR, DR, TTP or OS between EBV-positive and EBV-negative PTLD. On the other hand, response to 4 applications of rituximab was a highly significant predictor of OS, TTP and progression-free survival (PFS) despite treatment stratification (all p<0.001). 37/148 patients (25%) achieved CR with 4 cycles of rituximab and were allocated to rituximab consolidation. In this group, TTP in the intention-to-treat population was significantly longer than in the corresponding group in the PTLD-1 trial (37 patients versus 14 patients, p<0.05). In the 111 patients allocated to R-CHOP consolidation, ORR was 78/92 (85%) with 55/92 (60%) complete remissions (89% and 60%, respectively, in PTLD-1). Median TTP was not reached, the 3-year estimate was 73% (69% in PTLD-1). In patients refractory to rituximab induction, the CR rate was 22/38 (58%) with R-CHOP compared to 3/11 (27%) in PTLD-1 with CHOP (p=0.07); median PFS was 1.4 years versus 0.3 years in PTLD-1, p<0.05. The frequency of grade 3/4 leukopenia and infections was 63% and 34%, respectively. Treatment-related mortality occurred in 7%. Conclusions: This largest trial cohort in PTLD to date demonstrates for the first time that treatment stratification by response to rituximab induction is feasible, safe and effective. Rituximab consolidation in early rituximab responders results in significantly better disease control compared to CHOP consolidation. The addition of rituximab to CHOP chemotherapy improves outcome in patients refractory to rituximab monotherapy. Disclosures Trappe: Mundipharma: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau. Zimmermann:Roche: Honoraria; Celgene: Other: Travel support. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Mollee:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zaucha:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau. Dührsen:Roche: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Hüttmann:Amgen: Research Funding; Roche: Research Funding. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau. Kliem:Astellas: Honoraria; Fresenius: Honoraria; Genzyme: Honoraria; Novartis: Honoraria; Roche: Honoraria; Raptor: Honoraria. Leblond:Janssen: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau. Choquet:Janssen: Consultancy; Roche: Consultancy.

A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7033-7033
Author(s):  
N. Helbekkmo ◽  
S. H. Sundtroem ◽  
U. Aaseboe ◽  
P. F. Brunsvig ◽  
C. L. Von Plessen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2, both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p<0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.

Prospective, multicenter, randomized GITMO-IIL trial comparing intensive (R-HDS) to conventional chemoimmunotherapy (CHOP-R) in high-risk follicular lymphoma (FL) at diagnosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8006-8006 ◽  
Author(s):  
M. Ladetto ◽  
F. De Marco ◽  
F. Benedetti ◽  
U. Vitolo ◽  
C. Patti ◽  
...  
Keyword(s):  
High Risk ◽  
Superior Performance ◽  
Phase Iii ◽  
Bulky Disease ◽  
Absolute Increase ◽  
Intention To Treat ◽  
Secondary Endpoints ◽  
Extranodal Disease ◽  
Ecog Ps

8006 Background: The GITMO-IIL trial evaluated if an intensified treatment with ASCT is better than conventional chemotherapy (both supplemented with Rituximab) in high-risk FL at diagnosis. Methods: Eligibility required a FL with aaIPI>1 or IIL>2 score and an age of 18–60. Primary endpoint was EFS. The analysis was intention to treat. Secondary endpoints were PFS, DFS, OS, rate and prognostic value of MR. R-HDS and CHOP-R have been already described (Ladetto et al ASH 2005, Rambaldi et al Blood 2002). Planned sample size was 240 to detect a 20% absolute increase in the 3-years EFS. However the trial was stopped at 136 pts due to R-HDS superiority in EFS at a planned interim analysis. Cross-over was allowed after CHOP-R failure. Centralized PCR-based molecular analysis was planned on BM cells. Results: Age, stage, LDH, bulky disease, B-symptoms ECOG PS, extranodal disease aaIPI, IIL and retrospectively assigned FLIPI were similar in the two arms. CRs were 59% with CHOP-R and 85% with R-HDS (p<0.001). At a median follow-up of 39 months EFS and PFS are 36% and 38% for CHOP-R and 66% and 72% for R-HDS. OS is 83% in each arm. 67% of relapsed R-CHOP pts underwent R- HDS. MRs were 44% after CHOP-R and 80% after R-HDS (p<0.001). MR was associated to a better PFS (p<0.001). Of note, 3yrs PFS of pts with or without MR was similar in the two arms (MR: 67% with CHOP-R and 76% with R-HDS) (no MR: 25% for CHOP-R and 32% for R-HDS). MR was the strongest independent prognostic factor for PFS, EFS and DFS by multivariate analysis. Conclusions: This is the first phase III trial including MR analysis in a high proportion of pts and comparing intensified versus conventional therapy in the rituximab age. This trial indicates that: a) R-HDS has a better EFS and PFS in truly high-risk FL patients; b) MR is the strongest outcome predictor available in FL; c) the similar outcome in pts achieving (or not achieving) MR, regardless of treatment received, indicates that the superior performance of R-HDS is mostly due to its superior MR rate. [Table: see text]

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