Rates of peripheral neuropathy (PN) in patients (Pts) with relapsed and refractory multiple myeloma (RRMM) treated with carfilzomib vs comparators in pivotal phase III trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8041-8041 ◽  
Author(s):  
Ruben Niesvizky ◽  
Vania Hungria ◽  
Joy Ho ◽  
Aleksandr Suvorov ◽  
Darrell White ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Free Survival ◽  
Pain Subscale ◽  
Patient Reported ◽  
Phase Iii Trials ◽  
History Of ◽  
Recent Phase ◽  
Clinical Trial Information

8041 Background: PN is a dose-limiting toxicity for some anti-MM agents, such as the proteasome inhibitor (PI) bortezomib (V). Carfilzomib (K), a novel irreversible PI associated with low PN, was evaluated in 2 recent phase 3 studies in RRMM pts. Methods: This analysis evaluated PN rates in ASPIRE (K [27 mg/m2]-lenalidomide [R]-dexamethasone[d] [KRd] vs Rd in relapsed MM; Stewart 2015) and ENDEAVOR (Kd [K 56 mg/m2] vs Vd in RRMM; Dimopoulos 2016). We evaluated grade ≥2 PN during treatment, patient-reported outcomes (PROs; QLQ-C30 pain, FACT/GOG-neurotoxicity subscales), and progression-free survival (PFS) in pts with BL history of PN. Results: In ASPIRE, grade ≥2 PN rate was low (8.9% [KRd] vs 8.0% [Rd]; Table). Pain subscale scores were similar between arms. Median PFS was longer with KRd vs Rd for pts with BL grade ≥2 PN. In ENDEAVOR, grade ≥2 PN rate during the study (prespecified key secondary endpoint) was significantly lower with Kd vs Vd (6.0% vs 32.0%; Table). Pts had significantly improved pain and neurotoxicity subscale scores with Kd vs Vd. PFS improved with Kd vs Vd in pts with BL history of grade ≥2 PN (Table). Conclusions: In ENDEAVOR, Kd resulted in less PN vs Vd; in ASPIRE, PN rate was similar for KRd vs Rd. PFS was longer with KRd and Kd vs Rd and Vd, respectively, including in pts with BL grade ≥2 PN. Improved pain and neurotoxicity outcomes with K may be attributed to better disease control and/or lower PN rates. Clinical trial information: NCT01568866, NCT01080391. [Table: see text]

Patient-reported outcomes (PROs) from the phase III IMspire150 trial of atezolizumab (A) + cobimetinib (C) + vemurafenib (V) in patients (pts) with BRAFV600+melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10073-10073
Author(s):  
Karl D. Lewis ◽  
Caroline Robert ◽  
Paolo Antonio Ascierto ◽  
Daniil Stroyakovskiy ◽  
Helen Gogas ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Completion Rates ◽  
Free Survival ◽  
Unresectable Stage ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Clinical Trial Information

10073 Background: In IMspire150, A+C+V significantly improved investigator-assessed progression-free survival vs placebo (Pbo)+C+V in previously untreated pts with unresectable stage IIIc/IV BRAFV600+melanoma. PRO data from this trial are now reported. Methods: 514pts were randomized 1:1 to 28-day cycles of A+C+V or Pbo+C+V. Pts received C+V in cycle 1; A or Pbo was added on days 1 and 15 from cycle 2 onward. Pts completed the EORTC QLQ-C30 questionnaire on day 1 of cycle 1 (baseline), days 1 and 15 of cycle 2 and cycle 3, day 1 from cycle 4 onward, within 28-d of treatment discontinuation, and ≤6 months post-treatment. Prespecified secondary PRO endpoints were time to confirmed deterioration (TTCD; defined as time from randomization to first ≥10-point decrease from baseline held for 2 consecutive assessments, or 1 assessment followed by death on treatment) in quality of life (QoL) and physical functioning (PF). Prespecified exploratory endpoints were TTCD in role functioning (RF); mean change from baseline and percentage of pts with a clinically meaningful change (≥10 points from baseline) in QoL, PF, and RF. Results: Questionnaire completion rates were > 80% for most of the treatment period. At baseline, mean QoL, PF, and RF scores were moderate to high (Table). At week 6 (cycle 2), following initiation of A, QoL, PF, and RF scores declined, but returned to near-baseline levels at week 10 (cycle 3) and were largely maintained until week 36 (cycle 10), when < 50% of pts contributed data. In this time, ≥56% pts in both arms did not experience a clinically meaningful deterioration in QoL, PF, and RF. TTCD on QoL (hazard ratio [HR] 1.23; 95% CI 0.90-1.67), PF (HR 1.27; 95% CI 0.93-1.74), and RF (HR 1.15; 95% CI 0.86-1.55) favored Pbo, but only one-third of pts overall experienced a confirmed deterioration. Conclusions: PRO data showed that A+C+V did not worsen QoL, PF, and RF in pts with advanced BRAFV600+melanoma, thus supporting its use as a treatment option. Clinical trial information: NCT02908672. [Table: see text]

scholarly journals P14.15 Benefit of Bevacizumab for recurrent glioblastoma. Results of 81 patients from a single institution

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii69-iii69
Author(s):  
O Absalyamova ◽  
G Kobiakov ◽  
G Agabekyan ◽  
A Poddubsky ◽  
A Belyashova ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Rapid Progression ◽  
Concomitant Disease ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Continuous Application

Abstract BACKGROUND No standard of care has been established for patients with progressive glioblastoma (rGBM). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We retrospectively analyzed own results of BEV treatment in rGBM. MATERIAL AND METHODS 81 patients progressed after radiotherapy plus concomitant and maintenance temozolomide (TMZ) and undergo BEV as monotherapy (BevMo, 11 patients) or in combinations (Irinotecan (BevI) - 53, lomustine (BevL)- 11, TMZ (BevT) - 6. Median age 54 years. Among them 33 patients were re-irradiated: 11 - radiosurgery (RS), 20 fractionated irradiation (RT), 2 - RS+RT. 33 patients continued BEV after progression with changing or adding cytostatic. PFS was calculated from the date of verification, PFS1 - from the date of 1-st progression, PFS2 - from the date of 2-nd progression. RESULTS Median PFS was 9.0 ([CI] 7.0–10.9) months. Median PFS1 was 10.5 ([CI] 8.1–12.9) months. In the BevMo, BevI, BevL, BevT group PFS1 was 15.7, 10.1, 10.5, 13.2 months, respectively, p=0.7. Objective response (OR) was reached in 34%, stable disease (SD) in 28%, progression (PD) in 37% patients. 16 patients stopped BEV without progression (4-patient`s decision, 7- doctor`s decision, 2 - adverse event, 3 - concomitant disease). Median time of BEV treatment was 11.6 months. Median BEV-free interval till progression was 3.7 months. 33 patients continued or restarted BEV after progression. Median PFS2 was 8.0 ([CI] 4.9–11.1) months. The median OS from the date of 1-st progression was 23.5 months ([CI] 18.7–27.4). In groups with RT, RS, RS+RT and no re-irradiarion OS was 24.6 ([CI] 17.6–31.5), 35.4 ([CI] 35.0–35.8), 17.8, 20.6 ([CI] 15.2–26.0), respectively, p=0.2. CONCLUSION OS in our group is outrageously high. Maintaining BEV after progression was effective. In our group BEV discontinuation led to rapid progression. The resumption of Bev with progression was effective, which indicates the advisability of its continuous application.

scholarly journals Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials

2018 ◽  
Vol 36 (25) ◽  
pp. 2585-2592 ◽  
Author(s):  
Cesare Gridelli ◽  
Alessandro Morabito ◽  
Luigi Cavanna ◽  
Andrea Luciani ◽  
Paolo Maione ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Health Status Score

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis

2017 ◽  
pp. 1-12
Author(s):  
Doah Cho ◽  
Felicia T. Roncolato ◽  
Johnathan Man ◽  
John Simes ◽  
Sarah J. Lord ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Predictors Of Success ◽  
Biologic Therapies ◽  
Therapeutic Success ◽  
Free Survival ◽  
Randomized Controlled ◽  
Phase Iii Trials

Purpose The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. Methods This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. Results Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively Conclusion Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.

Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer

Lung Cancer ◽  
2013 ◽  
Vol 79 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Etsuji Suzuki ◽  
Massimo Di Maio ◽  
Paolo Chiodini ◽  
Yoshiro Fujiwara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Targeted Agents ◽  
Small Cell Lung ◽  
Free Survival ◽  
Phase Iii Trials

Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17043-e17043
Author(s):  
I. Diaz de Corcuera ◽  
C. Serrano ◽  
J. Pérez ◽  
I. Quispe ◽  
M. Arguis ◽  
...  
Keyword(s):  
Randomized Study ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Good Alternative ◽  
Phase Iii ◽  
Single Institution ◽  
Free Survival ◽  
Recent Phase ◽  
Unfit Patients

e17043 Background: Results of a recent phase III randomized study with cetuximab and platin-5FU chemotherapy support its use in recurrent/metastatic SCCHN. However, many patients (pts) are not able to be treated with platin combinations. Paclitaxel (P) and cetuximab (C) have shown an encouraging activity in a similar patients subset. We review the data of the patients treated with this schedule in our centre. Methods: From our database, we conducted a retrospective study of 20 patients with recurrent SCCHN who did not meet criteria for platin therapy and were treated with weekly P (80 mg/m2) and C (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerable toxicity. We have collected data regarding previous treatments, response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity. Results: From January 2007 to November 2008, 20 patients were included (18 male, 2 female) with a median age of 63 (50–81). Oral cavity (35%) and oropharynx (25%) were the most frequent locations. Most of the pts (13/20) had been treated with previous chemotherapy combinations (range 1–3 lines). All pts were evaluable for response and toxicity. Overall RR was 45% (1CR, 8 PR) and 35% of the pts (7/10) had SD. Response in radiated areas were 35% (6/17). With a median follow up of 10 months the median PFS and OS were 6.5 and 7 months respectively. Main related toxicities (Gr 2/3) were acne-like rash (30%), asthenia (15%), anemia (10%), and mucositis (10%). Conclusions: Our analysis confirms that weekly paclitaxel-cetuximab is an effective and safety combination in metastatic/recurrent SCCHN. Treatment is very well tolerated and could be a good alternative to platin-based chemotherapy in unfit patients for this therapy. No significant financial relationships to disclose.

An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9013-9013 ◽  
Author(s):  
Axel Hauschild ◽  
Jean Jacques Grob ◽  
Lev V. Demidov ◽  
Thomas Jouary ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Independent Review ◽  
Clinical Trial Information

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]

The occurrence of grade 4 adverse events and survival outcomes in patients with nonsquamous non-small cell lung cancer receiving bevacizumab with chemotherapy in the phase III PointBreak and AVAiL studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Liza Cosca Villaruz ◽  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Larry Leon ◽  
Sebastien Hazard ◽  
...  
Keyword(s):  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e19022 Background: Progression-free survival (PFS) is a key trial end point for clinical practice, as it relates to a change of treatment line. Grade 4 progression-free survival (G4PFS; defined as time from treatment start to the earlier of progressive disease [PD], onset of a G4 adverse event [AE], or death from any cause) is a composite end point incorporating a measure of tolerability to PFS. This post hoc analysis evaluates G4PFS and the effect of G4 AEs on PFS and overall survival (OS) in patients (pts) enrolled in PointBreak (PB) and AVAiL. Methods: Pts in PB were randomized to bevacizumab (BEV) 15 mg/kg q3w with carboplatin and paclitaxel (CP) or pemetrexed (CPem) for ≤4 cycles. Eligible pts received either BEV or BEV + Pem q3w until PD or unacceptable toxicity. Pts in AVAiL received cisplatin and gemcitabine for ≤6 cycles and either placebo or BEV (7.5 or 15 mg/kg) q3w until PD. AEs were graded via NCI-CTCAE v3.0. Kaplan-Meier and Cox model methods were used to estimate medians and hazard ratios (HRs) for PFS, G4PFS, and OS. PFS and OS were also compared in each arm for pts with occurrence of a G4 AE before week 12 of treatment vs those without. Results: Of those receiving BEV, ~30% of AVAiL pts and 38% of PB pts had a G4 AE. Uncomplicated neutropenia was the most common G4 AE in the CP + BEV arm of PB (26%) and in the BEV arms of AVAiL (11%). PFS, G4PFS, and outcomes by G4 AE occurrence are shown (Table). Conclusions: In both the PB and AVAiL trials, median G4PFS was numerically shorter than median PFS. G4 AE occurrence, however, did not affect subsequent PFS or OS in either trial. Clinical trial information: NCT00762034 and NCT00806923. [Table: see text]

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