scholarly journals ACTR-32. NRG ONCOLOGY RTOG 1205: RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VS. BEVACIZUMAB ALONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi20-vi20 ◽  
Author(s):  
Christina Tsien ◽  
Stephanie Pugh ◽  
adam Dicker ◽  
Jeffrey Raizer ◽  
Martha Matuszak ◽  
...  
Keyword(s):  
Objective Response ◽  
Patient Characteristics ◽  
Recurrent Glioblastoma ◽  
Rank Test ◽  
Significance Level ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Recurrent Gbm

Abstract This study sought to determine whether re-irradiation (ReRT) and concurrent bevacizumab (BEV) improves overall survival (OS) compared to BEV alone in recurrent glioblastoma (GBM). Patients (pts) were randomized 1:1 to ReRT (35 Gy/10 fractions) plus BEV (IV 10 mg/kg q2 wks) vs. BEV alone. With 160 pts, there was 80% power to detect a 31% reduction in death hazard for BEV+RT at a one-sided significance level of 0.10 using a log rank test. OS and PFS were estimated by Kaplan-Meier and HRs estimated by exact binomial distribution. Objective response was assessed using MacDonald and RANO criteria. From 11/2012 to 4/2016, 182 pts were randomized, with 170 eligible, analyzable pts. 11 pts did not receive protocol treatment. Patient characteristics (age, KPS, re-resection rates) were balanced between arms. Median f/u for censored pts was 12.8 months (mos; min-max, 0.03–52.8). BEV+ReRT did not improve OS vs BEV alone, with median OS of 10.1 vs 9.7 mos, (HR=0.98, 95% CI=0.70–1.38, p=0.46). Median PFS for BEV+RT and BEV was 7.1 vs. 3.8 mos, respectively (HR=0.73, 95% CI=0.53–1.0, p=0.051). BEV+ReRT improved 6-mo PFS rate (PFS6): 54 vs. 29%, (HR=0.42, 95% CI=0.34–0.5, p=0.001). Overall, treatment was well tolerated: 5% acute and 0% delayed grade 3+ treatment-related AE. Most patients died from recurrent GBM. CONCLUSION: RTOG 1205 is the first, prospective, randomized multi-institutional study to evaluate the safety and efficacy of ReRT in recurrent GBM using modern RT techniques. Overall, ReRT was shown to be safe and well tolerated. BEV+ReRT did not demonstrate a benefit in OS but an improved PFS6, and clinically meaningful PFS improvement. Molecular correlates of response analyses are ongoing. Funded by U10CA180868, U10CA180822 from the National Cancer Institute.

scholarly journals Longitudinal analysis of quality of life following treatment with Asunercept plus reirradiation versus reirradiation in progressive glioblastoma patients

2019 ◽  
Vol 145 (3) ◽  
pp. 531-540
Author(s):  
Wolfgang Wick ◽  
Andriy Krendyukov ◽  
Klaus Junge ◽  
Thomas Höger ◽  
Harald Fricke
Keyword(s):  
Quality Of Life ◽  
Neurological Status ◽  
Recurrent Glioblastoma ◽  
Rank Test ◽  
Treatment Groups ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
The Central Nervous System ◽  
Eortc Qlq

Abstract Purpose Glioblastoma is an aggressive malignant cancer of the central nervous system, with disease progression associated with deterioration of neurocognitive function and quality of life (QoL). As such, maintenance of QoL is an important treatment goal. This analysis presents time to deterioration (TtD) of QoL in patients with recurrent glioblastoma receiving Asunercept plus reirradiation (rRT) or rRT alone. Methods Data from patients with a baseline and ≥ 1 post-baseline QoL assessment were included in this analysis. TtD was defined as the time from randomisation to the first deterioration in the EORTC QLQ-C15, PAL EORTC QLQ-BN20 and Medical Research Council (MRC)-Neurological status. Deterioration was defined as a decrease of ≥ 10 points from baseline in the QLQ-C15 PAL overall QoL and functioning scales, an increase of ≥ 10 points from baseline in the QLQ-C15 PAL fatigue scale and the QLQ-BN20 total sum of score, and a rating of “Worse” in the MRC-Neurological status. Patients without a deterioration were censored at the last QoL assessment. Kaplan–Meier estimates were used to describe TtD and treatment groups (Asunercept + rRT or rRT alone) were compared using the log-rank test. Results Treatment with Asunercept + rRT was associated with significant improvement of TtD compared with rRT alone for QLQ-CL15 PAL overall QoL and physical functioning, and MRC Neurological Status (p ≤ 0.05). In the Asunercept + rRT group, QoL was maintained beyond progresison of disease (PoD). Conclusion Treatment with Asunercept plus rRT significantly prolongs TtD and maintains QoL versus rRT alone in recurrent glioblastoma patients.

Efficacy and safety of sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC) and lung metastases (mets) only at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Nobuo Shinohara ◽  
Hideyuki Akaza ◽  
Yoshihiko Tomita ◽  
Takeshi Yuasa ◽  
Hiroyuki Fujimoto ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Objective Response ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15098 Background: The lungs may be the sole site of mets in RCC.In this retrospective analysis, we analyzed the efficacy and safety of SU in mRCC pts from a global phase (ph) III study and a Japanese ph II study who had lung mets only at baseline. Methods: In the ph III study, treatment (Tx)-naïve mRCC pts were randomized 1:1 to SU 50 mg/d on a 4-weeks-on-2-weeks-off schedule (n=375) or interferon-a (IFN) 9 MU subcutaneously TIW (n=360). In the single-arm ph II study, Tx-naïve (n=25) and cytokine refractory (n=26) mRCC pts received the same SU Tx. In the ph III study, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, with median values compared by log-rank test. In both studies, objective response rate (ORR) was calculated with a two-sided 95% CI. PFS, OS, ORR, and safety were analyzed at final data cutoff. Results: In the ph III study, 31 (8%) and 42 (11%) pts in the SU and IFN groups, respectively, had lung mets only, compared with 12 (24%) in the ph II study. Baseline characteristics in lung mets pts were similar to all pts. In lung mets pts from the ph III study, ORR was higher with SU than with IFN (58.1% [95% CI: 39.1–75.5] vs. 19.0% [95% CI: 8.6–34.1]; P<0.001); there was a trend for longer median PFS with SU (14.1 vs. 7.8 months; HR: 0.531 [95% CI: 0.278–1.015]; P=0.0513); and median OS was comparable in both Tx subgroups (HR: 0.739 [95% CI: 0.335–1.628]; P=0.4507), although, at 25% of events, median OS was 22.9 months with SU vs. 15.8 months with IFN. In lung mets pts from the ph II study, ORR was 75.0% (95% CI: 42.8–94.5); at the time of analysis, median PFS and OS had not been reached; 4 pts (33%) had died due to any cause and 8 (67%) were alive without disease progression. The most common grade ≥3 SU-related AEs were fatigue, hand-foot syndrome, and diarrhea (all 19%) in the ph III study, and decreased platelets (100%), white blood cells (92%), and neutrophils (92%) in the ph II study. Conclusions: In the ph III study, Tx-naïve mRCC pts with lung mets only had significantly higher ORR and a trend for improved PFS and OS with SU compared with IFN. In the Japanese ph II study, ORR with SU was 75% in lung mets pts. Thus, 1st-line use of SU in mRCC pts with lung mets should be encouraged.

Phase II study of PX-866 in recurrent glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Marshall W. Pitz ◽  
Mary Valeria MacNeil ◽  
David R. Macdonald ◽  
Ankineedu Saranya Kakumanu ◽  
Brian Thiessen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Stage I ◽  
Stage Ii ◽  
Response Data ◽  
Grade 3 ◽  
Recurrent Gbm

2051 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority of GBM have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the interim results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM at first recurrence after treatment with chemoradiation and adjuvant temozolomide are given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam are done every 8 weeks to determine treatment response. The trial has a 2-stage design with dual endpoints of objective response and early progression (within 8 weeks). In Stage I, 15 pts are evaluated and if 0 responses and 10 or more early progressions are seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for efficacy analysis. Tumour tissue is collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations). Results: Seventeen pts have been enroled to date: 14 evaluable for response and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females and 10 males. No pts had received treatment for recurrent GBM, and median time between initial diagnosis and study enrolment was 300 days (range: 113-447 days). Pts have received a median of one 8-week cycle of PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to disease progression and 3 due to grade 3/4 liver enzyme abnormalities. Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6 pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3), lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is not yet known if the trial will continue to Stage II. Archival tissue is available on all patients and is undergoing analysis. Conclusions: This is one of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has been relatively well tolerated. Stage I response data are premature; while it is not yet known if the criteria will be met to continue to Stage II, prolonged SD has been observed in some pts. The correlative biomarker assays underway will be important to understand this observation.

scholarly journals Reoperation rates for symptomatic nonunions in posterior cervical (subaxial) fusions with and without bone morphogenetic protein in a cohort of 1158 patients

2016 ◽  
Vol 24 (4) ◽  
pp. 556-564 ◽  
Author(s):  
Kern H. Guppy ◽  
Jessica Harris ◽  
Jason Chen ◽  
Elizabeth W. Paxton ◽  
Julie Alvarez ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Patient Characteristics ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Morphogenetic Protein ◽  
Significant Difference ◽  
Spinal Fusions ◽  
Reoperation Rates

OBJECTIVE Bone morphogenetic protein (BMP) was first approved in 2002 for use in single-level anterior lumbar fusions as an alternative to iliac crest grafts. Subsequent studies have concluded that BMP provides superior fusions rates and therefore reduces reoperations for nonunions. The purpose of this study was to determine the reoperation rates for symptomatic nonunions in posterior cervical (subaxial) spinal fusions with and without the use of BMP and to determine if the nonunion rates are statistically significantly different between the two groups. METHODS Between January 2009 and September 2013, the authors identified 1158 posterior cervical spinal fusion cases in the subaxial spine (C2–7) from a large spine registry (Kaiser Permanente). Patient characteristics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Reoperations for symptomatic nonunions were adjudicated via chart review. Logistic regression was conducted to produce estimates of odds ratios (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves for the non-BMP and BMP groups were generated and compared using the log-rank test. RESULTS In this cohort there were 1158 patients (19.3% with BMP) with a median follow up of 1.7 years (interquartile range [IQR] 0.7–2.9 years) and median duration to operative nonunion of 0.63 years (IQR 0.44–1.57 years). Kaplan-Meier curves showed no significant difference in reoperation rates for nonunions using the log-rank test (p = 0.179). In a subset of patients with more than 1 year of follow-up, 788 patients were identified (22.5% with BMP) with a median follow-up duration of 2.5 years (IQR 1.7–3.4 years) and a median time to operative nonunion of 0.73 years (IQR 0.44–1.57 years). There was no statistically significant difference in the symptomatic operative nonunion rates for posterior cervical (subaxial) fusions with BMP compared with non-BMP (1.1% vs 0.7%; crude OR 1.73, 95% CI 0.32–9.55, p = 0.527) for more than 1 year of follow-up. CONCLUSIONS This study presents the largest series of patients using BMP in posterior cervical (subaxial) spinal fusions. Reoperation rates for symptomatic nonunions with more than 1 year of follow-up were found to be 1.1% with BMP and 0.7% without BMP. There was no significant difference in the reoperation rates for symptomatic nonunions with or without BMP.

Histologic Grade Predicts Recurrence for Marginally Excised Canine Subcutaneous Soft Tissue Sarcomas

2009 ◽  
Vol 46 (5) ◽  
pp. 928-933 ◽  
Author(s):  
K. D. McSporran
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Tumor Recurrence ◽  
Soft Tissue Sarcomas ◽  
Rank Test ◽  
Survival Curves ◽  
Marginal Excision ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Grade 3

Local recurrence of marginally excised subcutaneous soft tissue sarcomas is variable and difficult to predict. This study aimed to identify predictors of local recurrence after excisional biopsy. Medical records of 236 dogs from which tumors had been received between 2004 and 2007 were analyzed. Medium- to large-breed dogs, median age 10 years, were most commonly affected. A total of 139 tumors were graded histologically: 71 were grade 1 (51%); 59, grade 2 (42%); and 9, grade 3 (7%). Of these, 34 tumors (25%) were completely excised, and 104 (75%) were marginally excised. None of 30 completely excised tumors with follow-up information recurred. Three of 41 grade 1 tumors (7%), 14 of 41 grade 2 tumors (34%), and 3 out of 4 grade 3 tumors recurred after marginal excision. Kaplan-Meier survival curves were generated to evaluate survival and the tumor-free interval. The log-rank test and log-rank test for trend were used for comparisons. Tumor recurrence-free intervals for dogs with grade 1 and 2 tumors and for those with grade 1 and 3 tumors differed significantly ( P = .0027 and .0001, respectively) and overall were inversely related to tumor grade ( P = .0007). Kaplan-Meier survival curves, regardless of recurrence, for patients with grade 1, 2, or 3 tumors treated by marginal excision did not differ significantly, and none differed from the survival curves of patients treated by complete excision. In conclusion, histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft tissue sarcomas. Clean margins predict nonrecurrence. Tumor recurrence did not significantly reduce survival time.

scholarly journals Impact of Recurrence Pattern in Patients Undergoing a Second Surgery for Recurrent Glioblastoma

2021 ◽  
Author(s):  
Francesco Pasqualetti ◽  
Nicola Montemurro ◽  
Isacco Desideri ◽  
Mauro Loi ◽  
Noemi Giannini ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Recurrent Glioblastoma ◽  
University Hospital ◽  
Rank Test ◽  
Recurrence Pattern ◽  
Kaplan Meier ◽  
Second Surgery ◽  
Non Local ◽  
The Impact ◽  
Recurrent Gbm

Abstract Background. The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to examine the impact of different patterns of GBM failure on patients’ survival and second surgery outcomes.Methods. Overall survival was assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves.Results. Contact with ventricles, a second surgery and meningeal spread had a statistically impact on patient survival after the diagnosis of GBM recurrence (P=0.032, P=0.019 and P<0.01, respectively). Patients with local recurrence had better survival than patients with non-local ones, 24.1 versus 18.2 months, respectively (P=0.015, HR=1.856 (1.130 -3.050). Considering the cohort as a whole, the second surgery conferred an advantage in recurrent survival respect to non-operated patients. However, this advantage was more evident in patients with local recurrence (P=0.002 with HR 0.212 (95% CI 0.081-0.552) and P=0.029 with HR=0.522 (95% CI 0.291-0.936), respectively). Conclusions. The local recurrence pattern could be a promising field of interest for patients with recurrent GBM suitable for a second surgery.

Planned interim analysis of the intergroup FFCD-GERCOR-FNCLCC-AERO phase III study comparing two sequences of chemotherapy in locally advanced or metastatic gastric cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4533-4533 ◽  
Author(s):  
R. Guimbaud ◽  
O. Bouché ◽  
C. Rebischung ◽  
F. Bonnetain ◽  
C. Louvet ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Final Analysis ◽  
Phase Iii ◽  
Rank Test ◽  
Test Results ◽  
Significance Level ◽  
Kaplan Meier ◽  
Phase Iii Study ◽  
Grade 3

4533 Background: There are several standard chemotherapies in locally advanced or metastatic gastric or cardia adenocarcinoma, including ECF. Methods: Patients (pts) with a gastric or cardiac adenocarcinoma, locally advanced or metastatic, not surgically curable, with a WHO PS ≤2 and evaluable or measurable lesions, were randomized (1:1) according to the following sequences: ECC (epirubicin 50 mg/m2 D1+ cisplatin 60 mg/m2 D1 + capecitabine 2000 mg/m2 D2 to D15, every 3 weeks) in 1st line, then FOLFIRI (IRI 180 mg/m2 D1, leucovorin 400 mg/m2 D1, bolus 5FU 400 mg/m2 D1 and continuous 5FU 2400 mg/m2 in 46h, every 2 weeks) in 2nd line (Arm A) vs the reverse sequence (Arm B) with a stratification for center, PS, adjuvant treatment, site, linitis and measurable disease. To show an improvement in median time to treatment failure for the 1st line (TTF: time between randomization and progression, or treatment discontinuation or recurrence or death) of 15 to 20 weeks for arm B (α bilateral 5%; β 20 %), 381 failures and 416 pts are required in 4-year period. An interim analysis is planned when at least 190 failures are observed (ITT). TTF is estimated according to the Kaplan Meier method and compared with a Log-rank test. Results: In arm A and B, 174 and 175 pts were included respectively, between 17/06/05 and 21/12/07. Pts characteristics are: PS 1: 51%, med. age 60 years, gastric 67%, M+ 88%, resected primary tumor 27% and linitis 23%. In arms A and B respectively, 141 and 147 pts received at least one dose in 1st line and 61 and 44 pts in 2nd line. Toxicities during the first line is more frequent in the ECC than in the FOLFIRI arm: grade 3/4 (88 vs 68% - p ≤0.0001) and grade 3/4 hemato toxicities (69 vs 36% - p ≤0.001). In 2nd line, toxicities frequency is not different in both arms. The median TTF in 1st line (n = 310 pts) is 4.7 months [3.8 - 5.7] for ECC and 5.2 months [4.4–6.0] for FOLFIRI (Log Rank p = 0. 78). Regarding the 252 failures observed (67% of the required events), the significance level to reject H0 is p = 0.012 (EAST V5). Conclusions: It is not possible yet to conclude to the superiority of FOLFIRI in 1st line; the final analysis after observation of 381 failures is required. Regarding toxicity, hemato-toxicity is more frequent with ECC in 1st line. [Table: see text]

Clinical outcomes of the combination of bevacizumab and ttfields in patients with recurrent glioblastoma: Results of a phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Jaleh Fallah ◽  
Rekha T. Chaudhary ◽  
Lisa R. Rogers ◽  
Wei Wei ◽  
Cathy J. Brewer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Muscle Weakness ◽  
Phase Ii ◽  
Day Treatment ◽  
Recurrent Glioblastoma ◽  
Phase Ii Clinical Trial ◽  
Rank Test ◽  
Grade 3 ◽  
Recurrent Gbm

2537 Background: Clinical trials of bevacizumab monotherapy and TTFields monotherapy have shown activity but limited clinical benefit in patients (pts) with recurrent glioblastoma (GBM), with median progression-free survival (PFS) of 2-4 months and median overall survival (OS) of 6-9 months with either treatment modality. In a single-arm phase II clinical trial, the efficacy of the combination of bevacizumab and TTFields in pts with recurrent GBM was investigated. Methods: Pts with histologically confirmed GBM or other grade IV gliomas, who had disease progression after chemoradiation were enrolled in a phase II trial of the combination of bevacizumab and TTFields. Bevacizumab was given at a dose of 10 mg/Kg intravenously every 2 weeks and TTFields was worn by the pts continuously for more than 18 hours per day. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints were PFS at 6 months and OS at 12 months. Survival outcomes were assessed using the Kaplan-Meier method and compared by log rank test. Treatment-related adverse events were reported according to CTCAE, v4.0 criteria. Results: From April 2013 to December 2017, 25 pts were enrolled and 23 were evaluable: 18 (78%) men and 5 (22%) women, median age 60 years (range 17–78). 21 pts were Caucasian, 1 was African American and 1 of unknown race. After a median follow up of 31.6 months (range: 4.1-59.0 months), 21 out of 23 pts died (4 women and 17 men). The median PFS was 4.1 months (95%CI, 3.6-9.5) and the median OS was 10.5 months (95% CI, 8.2-14.9). The PFS rate at 6 and 12 months were 33% and 19%, respectively. The OS rate at 6 and 12 months were 82% and 46%, respectively. Women had better OS and PFS compared to men, however, the difference was not statistically significant which can be due to the small study population (table). Grade 3 and 4 toxicities considered definitely or probably related to the treatment included hypertension (n = 1) and cerebral infarction (n = 1). Other reported grade 3-4 toxicities (n = 7) included cough, dysphagia, muscle weakness, hyperglycemia, psychosis, seizure, lymphopenia, transaminitis, and muscle weakness considered unlikely to be treatment-related. Conclusions: The combination of bevacizumab and TTFields in is safe and feasible and has clinical efficacy in pts with recurrent GBM. Clinical trial information: NCT01894061 . [Table: see text]

A randomized, phase II trial comparing sequential paclitaxel/cisplatin/gemcitabine/vinorelbine/ (PCGV) with cisplatin/gemcitabine/vinorelbine/ (CGV) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17008-17008
Author(s):  
J. De Castro ◽  
C. Belda-Iniesta ◽  
E. Casado Saenz ◽  
J. Feliu ◽  
M. Sereno ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Rank Test ◽  
Time To Progression ◽  
Who Grade ◽  
Log Rank Test ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Nsclc Patients

17008 Background: New effective therapies are needed to improve the outcome of patients with advanced NSCLC. In this regard, new approaches such as cisplatin-based triplets have been explored with promising results but high toxicity. Furthermore, sequential chemotherapy schedules with taxanes followed by cisplatin-based regimens or viceversa could improve activity. A phase II study showed that sequential chemotherapy with weekly paclitaxel followed by CGV was highly active. Methods: A multicenter, randomized phase II trial of PCGV vs CGV in advanced NSCLC patients was conducted. Primary end-point: time to progression and survival. Eligible pts had unresectable, histologically confirmed NSCLC; no prior chemotherapy; PS 0–2; measurable disease. Pts received: Arm A (PCGV): P 150 mg /m2/week × 6, followed 2 weeks later by C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Arm B (CGV): C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Results: 106 Pts were included. Pts baseline characteristics (A/B: 52/54): male 82/79%; median age 60/59 (range 38–75 years); PS 0: 30/33%; 1 63/60%; 2: 7/7%; % squamous carcinoma:44/42%.WHO grade 3–4 toxicities for P were: neutropenia 18%; anemia 10%; thrombocytopenia 2%, peripheral neuropathy 18%. Grade 3–4 toxicities for CGV after P were: neutropenia 31%,nausea-vomiting 20%,thrombocytopenia 7%,anemia 5%,peripheral neuropathy 21%. WHO grade 3–4 toxicities for arm B were: neutropenia 35%,nausea-vomiting 19%, anemia 12%, thrombocytopenia 11% and peripheral neuropathy 15%. After therapy with arm A, 44% achieved a partial response, 15% had stabilization and 41% progressed. Arm B response rate were as follows: partial response 33%, stable disease 24% and progressive disease 43%. Median time to progression was (A/B) 7/6 months (log rank test, p 0.13) and median survival was (A/B): 11/10 months (log rank test, p 0.5). Conclusions: In spite of high response rate in TCGV arm, no survival benefit was detected in advanced NSCLC patients. No significant financial relationships to disclose.

CALGB 90601 (Alliance): Randomized, double-blind, placebo-controlled phase III trial comparing gemcitabine and cisplatin with bevacizumab or placebo in patients with metastatic urothelial carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4503-4503 ◽  
Author(s):  
Jonathan E. Rosenberg ◽  
Karla V. Ballman ◽  
Susan Halabi ◽  
Colleen Watt ◽  
Olwen Mary Hahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Primary Endpoint ◽  
Objective Response ◽  
Phase Iii ◽  
Adverse Event Rate ◽  
Rank Test ◽  
Prior Chemotherapy ◽  
Log Rank Test ◽  
Metastatic Urothelial Carcinoma ◽  
Grade 3

4503 Background: The combination of gemcitabine (G) and cisplatin (C) is a standard therapy for metastatic urothelial carcinoma (mUC). Based on data that angiogenesis plays a role in UC growth and progression, a randomized placebo-controlled trial was performed. Methods: Patients mUC, no prior chemotherapy for metastatic disease and >12 months from prior (neo)adjuvant chemotherapy and ECOG PS 0-1 were randomized 1:1 to G 1000 mg/m2 IV days 1 and 8 and C IV 70 mg/m2 day 1 with bevacizumab (GCB) 15 mg/kg IV or placebo (GCP) day 1 every 21 days. Randomization was stratified by the presence of visceral metastases and prior chemotherapy. The primary endpoint was overall survival (OS) defined as the time from randomization to death or last follow-up (FU). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and ≥ grade 3 toxicity. With 445 deaths, the log-rank test had an 87% power to detect a hazard ratio (HR) of 0.74 with a 2-sided α=0.05. The primary analysis was based on the stratified log-rank test adjusting on stratification factors. Alliance Data Safety and Monitoring Board approved the final OS analysis be performed at 420 events due to lower than expected event rates. Results: 506 patients were randomly assigned (252 GCB, 254 GCP) stratified by the presence of visceral disease and prior chemotherapy for UC. The median FU for patients still alive was 46.2 months. Median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP with a HR of 0.87 (95%CI 0.72-1.06; 2-sided Wald p=0.17). The HR for PFS was 0.77 (95%CI 0.63-0.93) in favor of GCB (p=0.0074). Grade 3 or greater adverse event rate was 83.5% with GCB compared to 80.7% with GCP. Conclusions: The addition of bevacizumab to GC chemotherapy did not result in improved OS (primary endpoint) in patients with mUC but there was a PFS improvement. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy. Support: U10CA180821, U10CA180882, U10CA180820, U10CA180853, U10CA180888, Genentech https://acknowledgments.alliancefound.org. Clinical trial information: NCT00942331.

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