A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

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.

Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 204-204
Author(s):  
Keisho Chin ◽  
Ken Kato ◽  
Byoung Chul Cho ◽  
Masanobu Takahashi ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Special Interest ◽  
Safety Data ◽  
Phase Iii ◽  
Taxane Chemotherapy ◽  
Favorable Safety ◽  
Safety Signals

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.

scholarly journals Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial

2020 ◽  
Vol 38 (31) ◽  
pp. 3592-3603 ◽  
Author(s):  
D. Ross Camidge ◽  
Hye Ryun Kim ◽  
Myung-Ju Ahn ◽  
James C. H. Yang ◽  
Ji-Youn Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Interim Analysis ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Once Daily ◽  
Alk Inhibitor ◽  
Alk Positive

PURPOSE Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor–naive ALK-positive non–small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501 ). We report results of the second prespecified interim analysis (150 events). METHODS Patients with ALK inhibitor–naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected. RESULTS Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration–time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69). CONCLUSION Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.

Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA4504-CRA4504 ◽  
Author(s):  
P. R. Warde ◽  
M. D. Mason ◽  
M. R. Sydes ◽  
M. K. Gospodarowicz ◽  
G. P. Swanson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Disease Specific Survival ◽  
Locally Advanced Prostate Cancer ◽  
Combined Modality ◽  
Disease Specific

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA > 40 μ g/l (119) or T2 PSA > 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.

A phase II study of cisplatin (P), S-1 (S), and concurrent thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (LA-NSCLC): Okayama Lung Cancer Study Group trial 0501.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7042-7042
Author(s):  
Daizo Kishino ◽  
Naoyuki Nogami ◽  
Yoshihiko Segawa ◽  
Keisuke Aoe ◽  
Hiroshi Ueoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Data ◽  
Response Rate ◽  
Locally Advanced ◽  
Active Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Lung Cancer Study Group ◽  
Sensitizing Effect

7042 Background: We previously reported an efficacy and safety of fractionated schedule ofP and docetaxel (D) (days 1, 8, 29, and 36, each) and concurrent TRT (DP-TRT) for LA-NSCLC (JCO 2010). Although the median survival time (MST: 26.3 months) was excellent, grade 3 or greater pneumonitis (10%) and esophagitis (14%) were observed and treatment-related death was 3%.Thus, further improvement in the safety as well as efficacy is strongly warranted. S, an oral fluoropyrimidine, is a new active agent possessing a radio-sensitizing effect. Additionally, combining S and P offered an active and safe regimen for metastatic NSCLC. The objective of this study was to assess the efficacy and safety of S + P with concurrent TRT for LA-NSCLC. Methods: Patients with stage IIIA/IIIB, aged ≤75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was response rate (RR), and required sample size was 48 patients. Results: Between 2006 and 2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1, 36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). The response rate was higher in older patients (≥65 yrs) than younger (<65 yrs) (89% vs. 64%, p=0.041). At a median follow-up of 40 months, median progression-free survival and MST were 9.3 months and 31.3 months, respectively. No difference in efficacy (response and survivals) was observed stratified by histology (sq vs. non-sq). Toxicities were generally mild, including G3/4 neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia (8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No toxic deaths occurred. Conclusions: This chemoradiotherapy regimen yielded a favorable overall survival data. Also, it was well-tolerated in patients with LA-NSCLC as compared with concurrent DP-TRT therapy especially in term of TRT-related toxicities. A phase III trial of this regimen vs. DP-TRT is now planned.

Overall survival in patients with lung cancer using a web-application-guided follow-up compared to standard modalities: Results of phase III randomized trial.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA9006-LBA9006 ◽  
Author(s):  
Fabrice Denis ◽  
Claire Lethrosne ◽  
Nicolas Pourel ◽  
Olivier Molinier ◽  
Yoann Pointreau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Supportive Care ◽  
Cancer Patients ◽  
Web Application ◽  
Phase Iii ◽  
P Value ◽  
Lung Cancer Patients

LBA9006 Background: We developed a web-application for an early detection of symptomatic relapse, complications and early supportive care in high-risk lung cancer patients between visits. A dynamical analysis of the weekly self-reported symptoms automatically triggered physician visit. Methods: We performed a national multi-institutional phase 3 prospective randomized study to compare web-application follow-up (experimental arm) for which patient’s self-scored symptoms that were weekly sent (between planned visits) to the oncologist and a clinical routine assessment with a CT-scan (every 3-6 months or at investigator’s discretion - standard arm). High risk lung cancer patients without progression and with a 0-2 performance status (PS) after an initial treatment were included. Maintenance chemotherapy or TKI therapy were allowed. In the experimental arm, an email alert was sent to the oncologist when some predefined clinical criteria were fulfilled: an imaging was then quickly prescribed. Early supportive cares were provided if adequate. The primary endpoint was to detect an improvement of 12% in 9 months survival in favor of the experimental arm (α = 5%, β = 20%, unilateral test). The boundary for declaring superiority with respect to overall survival at the pre-planned interim analysis was a p-value of less than 0.006. The PS at relapse, the quality of life (QOL) and cost-effectiveness were also investigated. Results: 121 patients were included in the intent-to-test survival analysis (90% were stage III/IV, median age: 65 y): 60 (61) in the experimental (standard) arms with equivalent baseline characteristics. Median follow-up was 9 months. Median overall survival in months was 19 (11.8), p=0.0014 (n  =  121; HR  =  0.33; 95 % CI, 0.16-0.67) and the PS at the first relapse was 0-1 for 81.5% (35.3%) of the patients (p<0.001) in the experimental (standard) arm. Conclusions: This trial shows a significant survival improvement using Web-application-guided follow-up that allowed better PS at relapse, earlier supportive care and reduction of routine imaging. QOL and cost analysis results will be presented during the meeting. Clinical trial information: NCT02361099.

Vandetanib with pemetrexed in patients with previously treated non-small cell lung cancer (NSCLC): An open-label, multicenter phase I study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7654-7654 ◽  
Author(s):  
R. De Boer ◽  
J. Vansteenkiste ◽  
Y. Humblet ◽  
J. Wolf ◽  
L. Nogova ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Electrolyte Imbalance ◽  
Smoking History ◽  
Qtc Interval ◽  
Duration Of Treatment ◽  
Open Label ◽  
Short Baseline ◽  
Once Daily

7654 Background: Vandetanib (ZD6474) is a once-daily oral anticancer drug that selectively inhibits VEGF-dependent tumor angiogenesis and EGFR- and RET-dependent tumor cell proliferation and survival. Methods: Eligible patients had locally advanced or metastatic NSCLC (stage IIIB/IV) after failure of 1st-line chemotherapy. An initial cohort of 10 patients received once- daily oral vandetanib (100 mg) with pemetrexed (500 mg/m2 i.v. infusion every 21 days). If <2 patients experienced a vandetanib- related dose-limiting toxicity (DLT), an additional cohort received vandetanib 300 mg + pemetrexed. The planned duration of treatment was =6 weeks. The primary objective of the study was to establish the safety and tolerability of vandetanib + pemetrexed. Secondary objectives included an assessment of pharmacokinetic (PK) interaction and preliminary assessment of efficacy (RECIST). Results: Twenty- one patients (14 male, 7 female; mean age 60 years, range 44–77) received vandetanib 100 mg + pemetrexed (n=10) or vandetanib 300 mg + pemetrexed (n=11). One DLT was reported in each cohort: QTc prolongation (>100 ms from baseline, but absolute QTc <500 ms) in a male patient who had electrolyte imbalance and short baseline QTc interval of 318 ms (100 mg cohort); and interstitial lung disease, which resolved after steroid therapy, in a Caucasian female patient with bronchoalveolar carcinoma and a long smoking history (300 mg cohort). The most common adverse events (AEs) were rash, anorexia, fatigue and diarrhea (all n=10; 48%). The most frequent CTC grade 3/4 AEs were increased gamma-glutamyltransferase (n=4), anorexia (n=3) and dyspnea (n=3), which are generally consistent with previous experience with vandetanib and pemetrexed as monotherapies. There was no apparent PK interaction between vandetanib and pemetrexed. In 18 patients evaluable for efficacy, there was one confirmed partial response (female; 100 mg cohort) and 13 stable disease =6 weeks. Conclusions: In patients with advanced NSCLC, vandetanib + pemetrexed was generally well tolerated, with no apparent PK interaction. A Phase III trial of vandetanib 100 mg + pemetrexed in 2nd-line NSCLC has begun. No significant financial relationships to disclose.

Phase I evaluation of vandetanib with radiation therapy (RT) ± cisplatin in previously untreated advanced head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6016-6016 ◽  
Author(s):  
V. Papadimitrakopoulou ◽  
S. J. Frank ◽  
G. R. Blumenschein ◽  
C. Chen ◽  
M. Kane ◽  
...  
Keyword(s):  
Phase I ◽  
Tyrosine Kinases ◽  
Locally Advanced ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Once Daily ◽  
Open Label Phase ◽  
To Receive

6016 Background: Vandetanib is a once-daily oral anticancer agent that selectively targets VEGF, EGF and RET receptor tyrosine kinases. We report preliminary results from an ongoing open-label phase I study of vandetanib with RT ± cisplatin in patients (pts) with previously untreated, unresected, locally advanced (stage III-IV) HNSCC. Methods: Eligible pts received once-daily vandetanib for 14 days followed by either 1) concomitant vandetanib + RT (2 Gy/d, 5 d/wk; total 70 Gy) + cisplatin (30 mg/m2, 2 h iv infusion/wk) for 7 wks, or 2) concomitant vandetanib + RT (2.2 Gy/d accelerated fractionation, 5 d/wk; total 66 Gy) for 6 wks. The primary objective was to determine the safety, tolerability and maximum tolerated dose (MTD) of vandetanib in both regimens. The first pt cohort received vandetanib 100 mg/day; escalation to 200 mg and 300 mg in subsequent cohorts was permitted providing <2/6 (33%) pts in the preceding cohort experienced a dose-limiting toxicity (DLT). Cohort expansion at the MTD of vandetanib was also planned. Results: As of Dec 1 2008, 24 pts (median age 53.5 yrs; 19 male; all M0) had received treatment with vandetanib + RT + cisplatin (n=18) or vandetanib + RT (n=6). In the triplet arm, no DLTs occurred in the initial vandetanib 100 mg cohort (n=6); an additional 6 pts were enrolled to receive vandetanib 200 mg but this dose was considered to exceed the MTD since DLTs were reported in 3/5 evaluable pts (Table). Vandetanib 100 mg was therefore declared the MTD with RT + cisplatin and cohort expansion at this dose continues. In regimen 2), 6 pts have received vandetanib 100 mg + RT and evaluation of this initial cohort is ongoing. Conclusions: This study, which continues to recruit, is the first to evaluate dual targeting of VEGFR/EGFR tyrosine kinases with chemoradiation or radiation alone in HNSCC pts. Among the 24 treated pts, 2 have completed the 2-year follow up, 1 death occurred that was causally related to cisplatin, and 21 remain in follow up or continue to receive treatment. [Table: see text] [Table: see text]

Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 559-559 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
Howard A. Burris ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Survival Data ◽  
Treatment Options ◽  
Safety Data ◽  
Phase Iii ◽  
Double Blind ◽  
Once Daily

559 Background: Current treatment options for postmenopausal patients with estrogen-receptor–positive (ER+) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BOLERO-2 trial supports the activity of everolimus (EVE; an oral mammalian target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in this patient population. Long-term PFS and survival data are awaited. Methods: BOLERO-2 is a phase III double-blind, randomized, international trial comparing EVE (10 mg once daily) plus EXE (25 mg once daily) versus placebo (PBO) plus EXE in postmenopausal women with advanced ER+ BC progressing or recurring after NSAIs (letrozole or anastrozole). Patients were randomized (2:1) to EVE + EXE or PBO + EXE. The primary endpoint was PFS by local investigator assessment. Main secondary endpoints included centrally assessed PFS, overall survival (OS), safety, bone turnover, and overall response rate (ORR). Results: Baseline disease characteristics including tumor burden and prior cancer therapy were well balanced between treatment arms (N = 724). Median PFS was doubled and response rates were consistently improved with EVE + EXE (n = 485) vs PBO + EXE (n = 239) in interim analyses. Median PFS by local assessment was ~3 mo with PBO + EXE vs 6.9 mo (hazard ratio [HR] = 0.43; P < .0001) and 7.4 mo (HR = 0.44; P < .0001) with EVE + EXE at 7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported with EVE + EXE (17.2%) vs PBO + EXE (22.7%) at 12.5 mo follow-up. Safety profiles were consistent with previous reports for mTOR inhibitors. PFS data including 528 events (protocol-specified final analysis), and updated OS and safety data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in patients with NSAI-refractory advanced ER+ BC. There were fewer deaths among patients receiving EVE, and further follow-up will evaluate the effect of EVE on OS.

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