scholarly journals Randomized Phase III Study Comparing Paclitaxel–Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983

2012 ◽  
Vol 30 (8) ◽  
pp. 792-799 ◽  
Author(s):  
Ronald de Wit ◽  
Iwona Skoneczna ◽  
Gedske Daugaard ◽  
Maria De Santis ◽  
August Garin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Group Versus ◽  
Progression Free Survival ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
Rank Test ◽  
Primary Analysis ◽  
Open Label ◽  
Number Of Patients

Purpose To compare the efficacy of four cycles of paclitaxel–bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m2 in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results Accrual was from November 1998 to April 2009. A total of 169patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.

Management of Advanced Germ Cell Cancer in Patients With Unfavorable Prognosis

2005 ◽  
Vol 3 (1) ◽  
pp. 77-83
Author(s):  
Kim Margolin
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
High Dose ◽  
Inadequate Response ◽  
Cell Transplant ◽  
First Line ◽  
Prognostic Features ◽  
Line Therapy

Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients with nonseminomatous tumors (NSGCT) and an even smaller percentage of seminoma patients are destined to have a less favorable outcome, due to an inadequate response to first-line chemotherapy (failure to achieve remission, finding of residual viable carcinoma at post-chemotherapy surgery, or relapse after achieving a remission). Despite the apparent salvage potential for regimens containing ifosfamide or paclitaxel, no proof exists that such combinations are superior to the standard regimen of four cycles of cisplatin, etoposide, and bleomycin (PEB) in the front-line therapy of patients with advanced NSGCT. Other modifications of first-line therapy, such as the addition of paclitaxel or the use of escalated doses of cisplatin, also have failed to increase the cure rate. The use of single or tandem cycles of high-dose chemotherapy (HDT with autologous hematopoietic cell transplant [aHCT]) in various settings (for selected patients with poor prognostic features before therapy, patients predicted to have a poor outcome based on the rate of serum tumor marker decline while on therapy, and patients in relapse or failure to achieve adequate response to standard therapy) has been evaluated in many phase II and a limited number of phase III trials, which are summarized in this review. Important questions that remain to be answered include the role of new agents and the use of more sophisticated techniques to understand prognostic and predictive factors in selecting therapy for GCT.

scholarly journals Low Survival in Poor Prognosis Metastatic Germ Cell Cancer in Belarus

2021 ◽  
pp. 63-71
Author(s):  
Alexander I. Rolevich ◽  
Denis M. Borodin ◽  
Anton N. Rabcheuski ◽  
Tatsiana A. Ivanitskaya ◽  
Sviataslau A. Semenov ◽  
...  
Keyword(s):  
Germ Cell ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Germ Cell Cancer ◽  
High Income ◽  
Collaborative Group ◽  
Entire Cohort

PURPOSE Since the development of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification in a 1997 study, high-income countries have reported a significant increase in survival for poor prognosis patients. There are scant data on IGCCCG risk-stratified survival from low- and middle-income countries. We assessed the progression-free survival (PFS) and overall survival (OS) rates in a contemporary cohort of Belarusian patients with advanced germ cell cancer (GCC) stratified by the IGCCCG prognostic classification and analyzed prognostic factors for survival. MATERIALS AND METHODS The consecutive cohort of patients with clinical stage IIb-III testicular GCC or extragonadal germ cell tumors who received treatment or consultation in our two centers between 2010 and 2015 was included. All patients underwent primary chemotherapy. The patients were divided into seminoma and nonseminomatous germ cell carcinoma (NSGCC) subgroups. The Kaplan-Meier method was used to estimate 5-year PFS and OS. RESULTS This study included 111 patients with a median age of 32 years, 95% of whom were diagnosed with testicular cancer. Seminoma and NSGCC were identified in 32 (29%) and 79 (71%) patients, respectively. The median follow-up was 6.1 years. The 5-year PFS and OS rates for the entire cohort were 70% and 77%, respectively. In patients with good prognosis seminoma and good, intermediate, and poor prognosis NSGCC, the estimated PFS rates were 76%, 88%, 74%, and 39% and those for OS were 83%, 97%, 83%, and 38%, respectively. CONCLUSION In our cohort of Belarusian patients with advanced germ cell tumors, we failed to demonstrate an improvement in PFS and OS compared with the 1997 IGCCCG study. Moreover, survival in poor prognosis group is inferior to that in IGCCCG and all contemporary series from high-income countries.

IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 267-267
Author(s):  
Richard S. Finn ◽  
Shukui Qin ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Treatment Benefit ◽  
Recist 1.1 ◽  
Open Label Phase ◽  
Phase Iii Study

267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

Quality of life and late toxicities in germ-cell cancer patients after high-dose chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4600-4600
Author(s):  
Thomas Wuendisch ◽  
Regina Naermann ◽  
Joerg Beyer ◽  
Anja Lorch ◽  
Keyword(s):  
Quality Of Life ◽  
Germ Cell ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
High Dose ◽  
Life Questionnaire ◽  
Myocardial Infraction

4600 Background: The number of long term survivors after treatment for relapsed/refractory germ cell cancer (GCC) is increasing but little is known about quality of life (QOL) and late toxicities (LT). Methods: We assessed LT and QOL in GCC patients (pts), treated in a prospective, randomized, multicenter, phase III trial comparing single versus sequential high-dose chemotherapy (HDCT) (Lorch 2007). All 216 pts were asked to complete the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to HDCT, 6 weeks after and yearly thereafter. Results were analyzed according to standard methods (Fayers 2001). In addition pts were contacted at a median of 76 months (range 45-109) after HDCT to obtain information about current social and professional activities as well as LT. Results: Among 216 pts, 92/216 (42%) were alive and without evidence of disease one year after randomization. Median age of pts was 34 years (range 15-56). A median of 4 conventional-dose cisplatin-based treatment cycles had been given prior to HDCT. Questionnaires and response to the survey were evaluable in 86/92 (93%) pts overall and in 59/86 (69%) pts more than 3 years after HDCT. Values for global health status, role functioning and emotional functioning declined during the first year after HDCT, increased in the following years, but did not reach the reference values from large samples of the general population in Norway (Hjermstad 1998). Pts after sequential HDCT scored better in a number of items (e.g. emotional-, cognitive-, social-functioning, fatigue and dyspnoea) in comparison to single HDCT including high-dose cyclophosphamide. Persisting polyneuropathy was reported in 59%, ototoxicity or tinnitus in 56%, erectile dysfunction in 24%, hypertension in 23%, hypercholesterinemia in 17%, diabetes mellitus in 6%, nephrotoxicity in 6%, myocardial infraction in 2% and second cancers in 1% of pts. Overall 82 % of pts were employed, 30% exercised regularly. Conclusions: HDCT has a negative impact on QOL, including social and professional life. Most common late toxicities were ototoxicity and polyneuropathy. Sequential HDCT without cyclophosphamide seems to result in a better outcome in respect to QOL.

Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA8003-LBA8003 ◽  
Author(s):  
Ralph Zinner ◽  
Helen J. Ross ◽  
Robert Weaver ◽  
Ramaswamy Govindan ◽  
Viran R. Holden ◽  
...  
Keyword(s):  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
Primary Objective ◽  
Phase Iii ◽  
Rank Test ◽  
Type I ◽  
Open Label ◽  
Grade 3

LBA8003 Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC. The primary objective was to compare progression-free survival without Grade 4 toxicity (G4PFS) between two vs three drug regimen arms. Methods: Patients ≥18 years, Stage IV NS NSCLC, AJCC (v7.0), and ECOG PS 0/1 were enrolled. Patients were randomized (1:1); received 4 cycles of induction (PemC: Pem, 500 mg/m2 and C, AUC = 6; PCB: P, 200 mg/m2, C, AUC = 6, and B, 15 mg/kg) followed by Pem (PemC Arm) or B (PCB Arm) maintenance therapy in the absence of progressive disease or discontinuation. Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS; assuming hazard ratio (HR) of 0.75; there was 80% power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10. Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables, and an exact test for ORR and DCR. Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment. Results: Patients were randomized to PemC (N = 182) or PCB (N = 179). Baseline factors were balanced between arms: median age 66/66 years; % female 42/42; % PS=0, 47/47; % stage IV M1a 29/30; for PemC vs PCB, median G4PFS (months) was 3.91/2.86 (HR = 0.85, 90% CI 0.7, 1.04, p = 0.176); PFS and OS had HR = 1.06 (95% CI 0.84, 1.35), p = 0.610, and HR = 1.07 (95% CI 0.83, 1.36), p = 0.616, respectively. The ORR (%) 23.6/ 27.4 and DCR (%) 59.9/57.0 were for PemC vs PCB, respectively. Significantly more drug-related grade 3/4 anemia (18.7% vs 5.4%), and thrombocytopenia (24.0% vs 9.6%) were seen on PemC; significantly more grade 3/4 neutropenia (48.8% vs 24.6%) and grade 1/2 alopecia (28.3 % vs 8.2%) were seen on PCB. Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two- vs three-drug regimens. There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm, and both regimens demonstrated tolerability. Clinical trial information: NCT00948675.

TIVO-3: A phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 541-541 ◽  
Author(s):  
Brian I. Rini ◽  
Sumanta K. Pal ◽  
Bernard Escudier ◽  
Michael B. Atkins ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Adverse Event ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Rank Test ◽  
Tyrosine Kinase Receptor ◽  
P Value ◽  
Risk Category ◽  
Open Label

541 Background: Tivozanib (T) is a biochemically potent and highly selective VEGF tyrosine kinase receptor inhibitor in clinical development in RCC. The TIVO-1 trial in treatment naïve or prior cytokine-treated subjects with metastatic (m) RCC showed a median progression free survival (mPFS) of 11.9 months (mos) for T compared to 9.1 mos for sorafenib (S) (p = 0.042, HR = 0.797). However, overall survival (OS) favored sorafenib, likely due to imbalanced crossover to active treatments. TIVO-3 was conducted to confirm the PFS results from TIVO-1. Methods: Subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI other than S or T, were stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized in a 1:1 ratio to T or S. The primary objective was to compare PFS by blinded independent radiological review. 350 subjects were enrolled to yield 244 events with ~88% power to detect a difference of 6 mos vs. 4 mos with a two-sided p-value of 0.05 by the log-rank test. Secondary endpoints were OS, safety, objective response rate (ORR), and duration of response. Results: The two arms were well balanced for demographics and prior cancer history.60% of subjects had 2 prior lines of therapy and 40% had 3 prior lines. 28% had prior treatment with a checkpoint inhibitor. T demonstrated a statistically significant improvement in mPFS compared to S, 5.6 (95% CI 7.3-5.3) v. 3.9 mos (95% CI 5.6-3.7; HR 0.73; p=0.02). PFS rate at 2 years was 18% for T compared to 5% for S. ORR was 18% for T compared to 8% for S. 44% of T treated subjects experienced a grade 3 treatment-related adverse event compared to 55% for S. Subjects on T were less likely to require a dose reduction (24% v. 38%), interruption (48% v. 63%), or discontinuation (21% v. 29%) due to an adverse event than subjects on S. Conclusions: T is superior to S as measured by PFS; 2-year PFS, and ORR in this pre-treated population and is better tolerated than S. OS data will be updated prior to presentation. Clinical trial information: NCT02627963.

A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Joyce F. Liu ◽  
Mark F. Brady ◽  
Ursula A. Matulonis ◽  
Austin Miller ◽  
Elise C. Kohn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Grade ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Based Chemotherapy

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O, or O alone, was superior to standard of care (SOC) plat-based therapy in relapsed plat-sensitive ovca. Methods: Eligible pts had recurrent plat-sensitive [ > 6-month plat-free interval (PFI)] high-grade serous or endometrioid, or BRCA-related, ovca. One prior non-plat therapy and unlimited prior plat-therapies were allowed; prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were exclusions. Pts were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily). Randomization was stratified by g BRCA status, PFI (6-12 vs > 12 months), and prior anti-angiogenic therapy. Target sample size was 549 pts; primary analysis occurred 2 years after the last pt enrolled. The primary endpoint was PFS. Type 1 error = 0.025 was controlled by a gatekeeping hierarchy that assessed C+O vs SOC, then O alone vs SOC, and finally C+O vs O. All maintenance therapy was prohibited. Results: Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had g BRCAmut. Median follow-up was 29.1 months. 53 pts on SOC initiated non-protocol therapy (predominantly PARP inhibitor maintenance) before disease progression. The hazard ratio (HR) for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) between C+O and SOC and 1.20 (95% CI 0.93-1.54) between O and SOC, with median PFS of 10.3, 8.2, and 10.4 months for SOC, O, and C+O, respectively. Response rates were 71.3% (SOC), 52.4% (O), and 69.4% (C+O). In gBRCA pts, HR for PFS was 0.55 (95% CI 0.73-1.30) for C+O vs SOC, and 0.63 (95% CI 0.37-1.07) for O vs SOC. In non-g BRCA pts, HR for these comparisons was 0.97 (95% CI 0.73-1.30) and 1.41 (1.07-1.86). No OS differences between arms were observed at 44% events. Pts receiving C+O (vs SOC) had more frequent Grade 3 or higher gastrointestinal (30.1% vs 8.4%), hypertension (31.7% vs 1.8%), and fatigue events (17.5% vs 1.8%). Conclusion: C+O demonstrated similar activity to SOC in relapsed plat-sensitive ovca but did not meet the primary endpoint of improved PFS. Clinical trial information: NCT02446600.

Sign in / Sign up

Export Citation Format

Share Document