KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
Javier Cortes ◽  
David W. Cescon ◽  
Hope S. Rugo ◽  
Zbigniew Nowecki ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Cox Regression ◽  
Phase Iii ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Kaplan Meier ◽  
Primary Endpoints ◽  
Immune Mediated ◽  
Locally Recurrent ◽  
Grade 3

1000 Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0. Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518 . Conclusion: Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns. [Table: see text]

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA4007-LBA4007 ◽  
Author(s):  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Final Analysis ◽  
Disease Status ◽  
Phase Iii ◽  
Controlled Study ◽  
Meaningful Improvement ◽  
Primary Endpoints ◽  
Positive Score ◽  
Combined Positive Score ◽  
Grade 3

LBA4007 Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC. Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583. [Table: see text]

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. LBA445-LBA445 ◽  
Author(s):  
Tamas Pinter ◽  
Steve Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

LBA445 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. This trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See Table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients (pts) with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) (NCT01809691).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5001-5001
Author(s):  
Neeraj Agarwal ◽  
Catherine Tangen ◽  
Maha H. A. Hussain ◽  
Shilpa Gupta ◽  
Melissa Plets ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Performance Status ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Meaningful Improvement ◽  
Intention To Treat ◽  
Grade 3

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]

Stomatitis incidence and its relationship with efficacy: A meta-analysis of everolimus clinical studies.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 151-151 ◽  
Author(s):  
Hope S. Rugo ◽  
James C. Yao ◽  
Marianne Pavel ◽  
Alain Ravaud ◽  
David Neal Franz ◽  
...  
Keyword(s):  
Cox Regression ◽  
Meta Analysis ◽  
Common Adverse Event ◽  
Phase 3 ◽  
Double Blind ◽  
Cox Regression Analysis ◽  
Her2 Breast Cancer ◽  
Kaplan Meier ◽  
Prophylactic Measures ◽  
Grade 3

151 Background: The most common adverse event (AE) with everolimus (EVE) is stomatitis. This meta-analysis evaluated the incidence, severity, and possible impact of stomatitis on efficacy in patients (pts) with cancer or tuberous sclerosis complex (TSC) who received EVE. Methods: Stomatitis events from 7 randomized, double-blind, phase 3 EVE studies included: RECORD-1 (RCC), RADIANT-2 (NET), RADIANT-3 (pNET), BOLERO-2 (HR+/HER2- breast cancer [BC]), BOLERO-3 (HER2+BC), and EXIST-1 and -2 (TSC). Time to first stomatitis occurrence and recurrence were analyzed using Kaplan-Meier (KM) methods. Stratified Cox regression analysis adjusted for baseline prognostic factors and corrected for confounding effect of duration of exposure was used to analyze association between stomatitis occurrence (≤ 8 wks of EVE start) and PFS in pts with cancer and response rate in pts with TSC. Results: This evaluation included EVE-treated pts with cancer (n = 1,455) and TSC (n = 157). Pts with cancer had stomatitis incidence of 66.9%, which occurred early, median 0.82 mo (95% CI, 0.7-1.0; 2-mo KM estimate 60.8%). 8.6% were grade 3/4 events. 1.7% of pts discontinued due to stomatitis. Stomatitis recurred in 40% of pts and appeared gradually. In pts with TSC similar results were observed. In EVE-treated pts, development of stomatitis was associated with longer PFS (corrected HR [95% CI]) in BOLERO-2 (0.78 [0.62-1.00]) and RADIANT-3 (0.70 [0.48-1.01]), and similar trend was observed in RECORD-1 (0.90 [0.66-1.22]) and RADIANT-2 (0.87 [0.61-1.22]), but not in BOLERO-3. In TSC, probably due to few pts, relationship between stomatitis and response was not conclusive. In all trials, pts on EVE had longer PFS vs placebo irrespective of stomatitis incidence. Conclusions: Stomatitis is observed frequently in initial wks of EVE therapy. Most AEs were grade 1/2 and manageable, rarely led to pt discontinuation. Stomatitis recurred in < 50% of pts. EVE-treated pts with cancer who had stomatitis achieved stable benefit similar to overall population, suggesting that continuing EVE is helpful. The importance of prophylactic measures in reducing EVE-induced stomatitis incidence and improving its management is being determined by ongoing studies.

scholarly journals Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000391
Author(s):  
Paolo Antonio Ascierto ◽  
Michelle Del Vecchio ◽  
Andrzej Mackiewicz ◽  
Caroline Robert ◽  
Vanna Chiarion-Sileni ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
Double Blind ◽  
Term Survival ◽  
Phase Iii Trial ◽  
Unresectable Stage ◽  
Registration Number ◽  
Grade 3

BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutantBRAFtumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively.ConclusionsThis 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies.Trial registration numberNCT01515189.

scholarly journals CTNI-29. CODEL: PHASE III TRIAL OF RT ALONE, RT PLUS TMZ, OR TMZ ALONE FOR NEWLY-DIAGNOSED, 1p/19q CODELETED ANAPLASTIC OLIGODENDROGLIOMA. ANALYSIS FROM THE INITIAL STUDY DESIGN. (NCCTG N0577, ALLIANCE)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii48-ii49
Author(s):  
Kurt Jaeckle ◽  
Karla Ballman ◽  
Martin van den Bent ◽  
Caterina Giannini ◽  
Evanthia Galanis ◽  
...  
Keyword(s):  
Cox Regression ◽  
Initial Study ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Phase Iii Trial ◽  
Grade 3 ◽  
Who Grade Iii ◽  
Grade Iii

Abstract BACKGROUND The original 3-arm CODEL design included a radiotherapy (RT)-alone control arm, an RT plus temozolomide (TMZ) arm, and an exploratory TMZ-alone arm. We report the analysis involving patients treated per the initial design. METHODS Adults (18+ years) with newly-diagnosed 1p/19q codeleted WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant TMZ (Arm B); or TMZ alone (Arm C). Primary endpoint was OS, Arm A vs. B. Secondary comparisons were performed for OS and PFS, comparing pooled RT arms with the TMZ-alone arm. RESULTS 36 patients were randomized equally to the three arms. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients had progressed, versus 37.5% (9/24) patients on the RT arms. PFS was shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) of RT-treated patients. OS did not statistically differ between arms, although this comparison was underpowered. After adjustment for IDH status (mutated vs. wildtype) in a Cox regression model, with IDH status and RT treatment status as co-variables (Arm C vs pooled A and B), PFS remained shorter for patients not receiving RT (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), and OS differences remained non-significant ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% patients (Arms A, B and C, respectively). Neurocognitive assessments, comparing baseline and 3 month timepoints, showed no significant differences between arms. CONCLUSIONS TMZ-alone treated patients experienced significantly shorter PFS than patients treated on the pooled RT arms, which remained significant when adjusting for IDH status. CODEL has been redesigned to compare the efficacy and toxicity of RT+PCV versus RT+TMZ. Clinicaltrials.gov Identifier: NCT00887146. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org.

Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide (EC or HEC) with cyclophosphamide, methotrexate, and fluorouracil (CMF) in 777 women with node-positive (N+) breast cancer (BC): 10-year follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
E. Azambuja ◽  
M. Paesmans ◽  
C. Bernard-Marty ◽  
M. Beauduin ◽  
A. Vindevoghel ◽  
...  
Keyword(s):  
Cox Regression ◽  
Menopausal Status ◽  
Survival Rates ◽  
Dose Intensity ◽  
Phase Iii ◽  
Open Label ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Primary Hypothesis

568 Background: The purpose of this presentation is to provide an update, with longer follow up data, of the results of this Belgian multicentric trial, which had shown a dose response curve for epirubicin at a median follow up of 4 years (Piccart et al, J Clin Oncol 2001; 19:3103–3110) Methods: In this prospective, open label, randomized trial of the 1990’s, patients aged from 18 to 70 years were stratified by center, 1–3 vs 4 or more nodes, and menopausal status (pre- vs postmenopausal). The primary hypothesis was that HEC could be associated with an increase in event-free survival (EFS) compared with CMF. Patients received CMF (oral cyclophosphamide days 1–14) for six cycles, EC (epirubicin 60 mg/m2, cyclophosphamide 500 mg/m2 day 1 every 3 weeks) for eight cycles or HEC (epirubicin 100 mg/m2, cyclophosphamide 830 mg/m2 day 1 every 3 weeks) for eight cycles. Tamoxifen followed chemotherapy in postmenopausal women with positive or unknown hormone receptor (HR). Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Results: The trial results are now updated, with an actuarial median follow-up of 12.2 years. Using Kaplan-Meier estimation, the 10-year EFS is 55% for patients who received CMF, 48% for EC patients, and 58% for HEC patients. The hazard ratios obtained from Cox regression models (HR) are, for EC vs HEC, 1.30 (95% confidence interval [CI], 1.02 to 1.67, P = .03); for CMF vs HEC, 1.12 (95% CI, 0.87 to 1.44, P = .39); and for CMF vs EC, 1.17 (95% CI, 0.92 to 1.48, P = .21). Kaplan-Meier estimates of the 10-year overall survival rates are 65% for patients who received CMF, 65% for EC patients, and 70% for HEC patients, with no significant differences among the three arms. Conclusions: The short term results of this trial are nicely confirmed at 10 years: in patients unselected for HR or HER-2 status, the dose intensity of epirubicin matters. Analysis in subsets of patients is ongoing, but will be only hypothesis-generating. [Table: see text]

Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients (pts) with advanced melanoma (MEL) (CheckMate 067).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
Jedd D. Wolchok ◽  
Vanna Chiarion-Sileni ◽  
Rene Gonzalez ◽  
Piotr Rutkowski ◽  
Jean Jacques Grob ◽  
...  
Keyword(s):  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Clinical Activity ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Primary Endpoints ◽  
Treatment Naïve ◽  
Grade 3

LBA1 Background: The results of a phase I study in MEL suggested complementary clinical activity with NIVO (a PD-1 checkpoint inhibitor) plus IPI (a CTLA-4 checkpoint inhibitor). Here, we report the results of a randomized, double-blind, phase III trial designed to evaluate NIVO combined with IPI or NIVO alone vs IPI alone in MEL. Methods: Treatment-naïve pts (N = 945) were randomized 1:1:1 to NIVO 1 mg/kg Q2W + IPI 3 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo, until progression or unacceptable toxicity. Pts were stratified by PD-L1 status, BRAF mutation status, and M-stage. Co-primary endpoints are progression-free survival (PFS) (reported here) and overall survival (pts continue to be followed). Secondary endpoints include objective response rate (ORR) by RECIST v1.1 and safety. Results: At a minimum follow-up of 9 months, NIVO + IPI and NIVO alone significantly improved PFS and ORR vs IPI (Table). Grade 3-4 drug-related adverse events (AEs) occurred in 55.0%, 16.3%, and 27.3% of pts in the NIVO + IPI, NIVO, and IPI arms, respectively (most commonly diarrhea [9.3%, 2.2%, 6.1%], increased lipase [8.6%, 3.5%, 3.9%], increased alanine aminotransferase [8.3%, 1.3%, 1.6%], and colitis [7.7%, 0.6%, 8.7%]). Drug-related AEs led to discontinuation in 36.4%, 7.7%, and 14.8% of pts in the NIVO + IPI, NIVO, and IPI arms, with 0, 1, and 1 drug-related deaths, respectively. Efficacy outcomes by PD-L1 status will also be presented. Conclusions: NIVO + IPI and NIVO alone had superior clinical activity vs IPI alone. The results with NIVO + IPI and NIVO alone further suggest complementary activity of the two agents. There were no new safety signals or drug-related deaths observed with the combination. Clinical trial information: NCT01844505. [Table: see text]

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