scholarly journals Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study

2021 ◽  
pp. JCO.21.00396
Author(s):  
Shaodong Hong ◽  
Yaxiong Zhang ◽  
Gengsheng Yu ◽  
Peijian Peng ◽  
Jiewen Peng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
End Point ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Phase Iii Study

PURPOSE GEM20110714 (ClinicalTrials.gov identifier: NCT01528618 ), the first randomized, phase III study of systemic chemotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC), reported significant progression-free survival improvement with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio, 0.55; 95% CI, 0.44 to 0.68; P < .001). Data from the final analysis of overall survival (OS) are presented here. METHODS From February 2012 to October 2015, 362 patients were randomly assigned to receive either GP (gemcitabine 1 g/m2 once daily on days 1 and 8 and cisplatin 80 mg/m2 once daily on day 1; n = 181) or FP (fluorouracil 4 g/m2 in continuous intravenous infusion over 96 hours and cisplatin 80 mg/m2 once daily on day 1; n = 181) once every 21 days. The primary end point was progression-free survival, which has been previously reported; OS was a secondary end point. RESULTS After a median follow-up time of 69.5 months with GP and 69.7 months with FP, 148 (81.8%) and 166 (91.7%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.72 (95% CI, 0.58 to 0.90; two-sided P = .004). The median OS was 22.1 months (95% CI, 19.2 to 25.0 months) with GP versus 18.6 months (95% CI, 15.4 to 21.7 months) with FP. The OS probabilities at 1, 3, and 5 years were 79.9% versus 71.8%, 31.0% versus 20.4%, and 19.2% versus 7.8%, respectively. Poststudy therapy was administered in 51.9% and 55.2% of patients in the GP and FP arms, respectively. CONCLUSION Among patients with previously untreated advanced nasopharyngeal carcinoma, those who receive GP have longer OS than those receive FP. Gemcitabine plus cisplatin should be considered a preferred front-line option for these patients.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Randomized phase III study of gemcitabine and cisplatin (GC) versus dose dense methotrexate, vinblastine, doxorubicin and cisplatin (DD-MVAC) in the perioperative setting for patients with locally advanced transitional cell cancer of the bladder: The French GETUG/AFU V05 VESPER trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS530-TPS530 ◽  
Author(s):  
Christian Pfister ◽  
Gwenaelle Gravis ◽  
Geraldine Pignot ◽  
Aude Flechon ◽  
Michel Soulie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cell Cancer ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Cancer Of The Bladder ◽  
Transitional Cell Cancer ◽  
Phase Iii Study

TPS530 Background: Radical cystectomy remains the gold standard treatment for invasive non metastatic transitional cell cancer of the bladder. Perioperative chemotherapy (adjuvant ou neoadjuvant) has been developed to increase overall survival. However, the chemotherapy administration time and optimal chemotherapy regimen are not yet determined. As DD-MVAC has been shown to be associated with higher response rates in bladder metastatic disease, also a better efficacy can be suspected in the perioperative setting. Methods: We designed a randomized phase III study to compare the efficacy of GC and DD-MVAC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after radical cystectomy (disease defined by a T2, T3 or T4a N0 M0 stadification for patients receiving neoadjuvant chemotherapy or pT3 or pT4 or pN+ and M0 for patients receiving adjuvant chemotherapy). Secondary endpoints include overall survival, side effects, response rate in the neoadjuvant setting. Main exclusion criteria were histological variants (pure adenocarcinoma or pure epidermoid carcinoma or pure or mixed small-cell neuro-endocrine carcinoma) and ventricular ejection fraction under 50%. The total number of patients projected was 500 based on the median progression-free survival rate of 50% at 3 years observed in patients treated with GC (standard arm A) in the perioperative setting. An absolute improvement of 10% (HR = 0.74) was expected with DD-MVAC (experimental arm B) with a = 0.05 and b = 0.20. In October 2017, 460 patients have been included. An interim analysis is planned after the occurrence of 174 events. With an estimated uniform accrual rate of 140 patients per year for 3.5 years and exponential survival, the final analysis is expected to occur 8 years after the start of the trial. Concomitant ancillary study has also started, focusing on the identification of subgroups for muscle invasive bladder tumors sensitivity to neoadjuvant chemotherapy, as suggested by the recent MDA classification. Clinical trial information: NCT 018 12369.

Impact of the prior chemotherapy with two different fluoropyrimidines on the efficacy of CapeIRI or FOLFIRI in metastatic colorectal cancer: An exploratory analysis of the phase III AXEPT trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 711-711
Author(s):  
Tae Won Kim ◽  
Kei Muro ◽  
Rui-hua Xu ◽  
Young Suk Park ◽  
Wei Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Oral Fluoropyrimidine ◽  
Significant Difference ◽  
Phase Iii Study ◽  
The Impact

711 Background: Modified CapeIRI (irinotecan 200 mg/m2 on day 1, capecitabine 1600 mg/m2 on days 1–14 every 3 weeks) with or without bevacizumab (± BV) has shown non-inferiority of overall survival compared with FOLFIRI ± BV based on the phase III study, AXEPT, as second-line chemotherapy for patients with mCRC. In this exploratory analysis of the AXEPT trial, we evaluated the impact of the prior chemotherapy with two different fluoropyrimidine backbones (fluorouracil and leucovorin vs oral fluoropyrimidine) on the efficacy of CapeIRI and FOLFIRI. Methods: Patients were randomized to receive standard FOLFIRI ± bevacizumab or modified CapeIRI ± bevacizumab after failure to fluoropyrimidine-based chemotherapy in the AXEPT study. Prior fluoropyrimidine backbones were categorized into oral fluoropyrimidine-based (eg, capecitabine or S-1) regimen (oral 5-FU group) and fluorouracil and leucovorin-based regimen (infusional 5-FU group). Assessed endpoints included overall survival, progression-free survival, response rate, and safety. Results: Prior fluoropyrimidine backbone was available for 642 patients among all 650 randomized patients (oral 5-FU group in 291, and infusional 5-FU group in 351). Median overall survival was 17.0 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 14.9 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Median progression-free survival was 7.9 and 8.6 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 6.8 and 8.3 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Conclusions: There was no significant difference in the efficacy of CapeIRI or FOLFIRI regardless of prior fluoropyrimidine backbones. Therefore, CapeIRI ± BV could also be effective for patients after failure of oral fluoropyrimidine-based chemotherapy (eg, CapeOX ± BV). Clinical trial information: NCT01996306. [Table: see text]

GEM20110714: Final overall survival results of the phase III study of first-line gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6521-6521
Author(s):  
Shaodong Hong ◽  
Yan Huang ◽  
Yunpeng Yang ◽  
Gengsheng Yu ◽  
Jun Jia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Group Performance ◽  
Performance Status ◽  
Randomized Study ◽  
Eastern Cooperative Oncology Group ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Study

6521 Background: GEM20110714, the first randomized, phase III study (NCT01528618) of systemic chemotherapy in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC), reported significant reduction of disease progression with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio [HR], 0.55; 95% CI, 0·44–0·68; P < .001). This study establishes GP as the standard-of-care for first-line treatment of R/M NPC. We present the final overall survival (OS) analysis here. Methods: In this multicenter, open-label study conducted in China, patients who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and R/M NPC were randomly assigned (1:1) to receive up to six cycles of either GP or FP once every 3 weeks. The primary endpoint was PFS, which has been previously reported; OS was a secondary endpoint. The final OS analysis was conducted with the data cutoff date of December 17, 2019. Results: After a median follow-up time of 64.4 months (95% CI, 61.1-67.6), 148 (81.8%) and 165 (91.2%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.723 (95% CI, 0.578 to 0.904; two-sided P = .004). The median OS was 22.1 months with GP versus 18.6 months with FP. The OS probabilities at 1, 3, and 5 years were 79.9% vs. 71.8%, 31.0% vs. 20.4%, and 18.5% vs. 7.6%, respectively. Un-predefined subgroup analyses based on baseline characteristics were consistent with the primary OS analysis. Postdiscontinuation systemic therapy use was similar: GP, 52%; FP, 57%. No new safety signals emerged. Conclusions: In patients with R/M NPC, GP is the first regimen to show significant improvement in OS in a phase III randomized study compared with a traditional chemotherapy regimen (i.e. FP). GP should be considered the standard treatment option for these patients. Clinical trial information: NCT01528618 .

Final Results of Phase III SYMMETRY Study: Randomized, Double-Blind Trial of Elesclomol Plus Paclitaxel Versus Paclitaxel Alone As Treatment for Chemotherapy-Naive Patients With Advanced Melanoma

2013 ◽  
Vol 31 (9) ◽  
pp. 1211-1218 ◽  
Author(s):  
Steven J. O'Day ◽  
Alexander M.M. Eggermont ◽  
Vanna Chiarion-Sileni ◽  
Richard Kefford ◽  
Jean Jacques Grob ◽  
...  
Keyword(s):  
Survival Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
End Point ◽  
Phase Iii Study ◽  
Induced Apoptosis

Purpose Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma. Patients and Methods Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m2 either alone or in combination with elesclomol 213 mg/m2 administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS. Results The study did not achieve its PFS end point (hazard ratio, 0.89; P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH. Conclusion The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.

Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

2018 ◽  
Vol 36 (8) ◽  
pp. 728-734 ◽  
Author(s):  
David S. Siegel ◽  
Meletios A. Dimopoulos ◽  
Heinz Ludwig ◽  
Thierry Facon ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Rank Test ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Risk Of Death ◽  
End Point ◽  
Grade 3

Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.

scholarly journals A multicenter randomized phase III study for newly diagnosed maximally resected glioblastoma comparing carmustine wafer implantation followed by chemoradiotherapy with temozolomide with chemoradiotherapy alone; Japan Clinical Oncology Group Study JCOG1703 (MACS study)

2019 ◽  
Vol 49 (12) ◽  
pp. 1172-1175
Author(s):  
Tomohiro Kadota ◽  
Ryuta Saito ◽  
Toshihiro Kumabe ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Carmustine Wafer ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints ◽  
Phase Iii Study

Abstract A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with &gt;90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].

scholarly journals Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study

2021 ◽  
pp. JCO.21.00217
Author(s):  
Yoon-Koo Kang ◽  
Suzanne George ◽  
Robin L. Jones ◽  
Piotr Rutkowski ◽  
Lin Shen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Control ◽  
Survival Data ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Once Daily ◽  
End Point ◽  
Significant Difference ◽  
Phase Iii Study

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha ( PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study ( NCT02508532 ), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER ( NCT03465722 ), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.

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