Efficacy and safety of the hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma (BCC): ERIVANCE BCC study update.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8579-8579 ◽  
Author(s):  
Aleksandar Sekulic ◽  
Michael R Migden ◽  
Anthony E Oro ◽  
Karl D Lewis ◽  
John D Hainsworth ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Primary Analysis ◽  
Molecule Inhibitor ◽  
The Us ◽  
Independent Review ◽  
One Year ◽  
Weight Decrease

8579 Background: The ERIVANCE BCC study is the pivotal trial of vismodegib (GDC-0449), a first-in-class small-molecule inhibitor of Hedgehog signaling, for treatment of locally advanced (laBCC) and metastatic BCC (mBCC), for whom there are no other effective therapy options. The study met the primary endpoint of overall response rate by independent review (Sekulic, Melanoma Res 2011). Here we report a 6-mo update of investigator-assessed (I-A) efficacy and safety endpoints as of May 26, 2011. Methods: This multicenter, international, nonrandomized 2-cohort study enrolled patients (pts) with laBCC (deemed inoperable or for whom surgery would be significantly disfiguring), and mBCC pts with RECIST-measurable disease. Pts received 150 mg oral vismodegib daily. Results: 104 pts (71 laBCC/33 mBCC) enrolled at 31 sites in the US, Europe, and Australia. I-A efficacy endpoints are shown in the table. One-year survival rate was 77.3% (95% CI 62.48–92.09%) for mBCC and 93.1% (95% CI 86.49–99.63%) for laBCC. Adverse events (AEs) in >30% of pts were muscle spasms, alopecia, dysgeusia, weight decrease, fatigue, nausea, and amenorrhea (33.3%; 2/6 pts). Serious AEs were reported in 32 pts (31%). No additional fatal AEs were reported since the prior data cut (n=7, 7%; none considered related to vismodegib). Conclusions: This 6-mo update of I-A efficacy and safety endpoints from the ERIVANCE BCC study supports the significant clinical benefit of vismodegib in both laBCC and mBCC reported at the primary analysis. Median DOR and PFS increased numerically with follow-up. The AE profile was consistent with the prior data cut. These results further support the efficacy of vismodegib for treatment of advanced BCC. [Table: see text]

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (aBCC): 18-month update of the pivotal ERIVANCE BCC study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9037-9037 ◽  
Author(s):  
Aleksandar Sekulic ◽  
Michael R. Migden ◽  
Nicole Basset-Seguin ◽  
Claus Garbe ◽  
Anja Gesierich ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Safety Data ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Hedgehog Pathway ◽  
Primary Analysis ◽  
Weight Decrease

9037 Background: Therapies for aBCC, which includes metastatic (m) and locally advanced (la) BCC, are limited. Abnormal Hedgehog pathway signaling is a key driver in BCC pathogenesis. Primary analysis of the pivotal ERIVANCE BCC trial of vismodegib, an oral hedgehog pathway inhibitor (HPI), demonstrated an objective response rate (ORR) of 30% and 43%, in mBCC and laBCC patients, respectively, with a median duration of response (DOR) of 7.6 months. We present safety and investigator (INV) assessed efficacy results 18 months (29 May 2012) after primary analysis (26 Nov 2010). Methods: Multicenter, international, nonrandomized study in patients (N=104) with radiographically measurable mBCC or laBCC (surgery inappropriate due to multiple recurrence, or substantial morbidity or deformity anticipated) receiving 150 mg oral vismodegib daily until disease progression or intolerable toxicity. Key secondary endpoints included INV-assessed ORR, progression-free survival (PFS), DOR, overall survival (OS), and safety. Results: At data cutoff, 21 patients continued to undergo protocol-specified assessments and 56 patients were in survival follow-up. The median dose intensity was comparable with primary analysis. ORR was 48.5%, mBCC; 60.3%, laBCC, comparable with primary analysis. However, median DOR improved (mBCC=14.7; laBCC=20.3 months). The median OS for mBCC was 30.9 months but not estimable in laBCC. Adverse events remained consistent, with muscle spasm, alopecia, dysgeusia, weight decrease, and fatigue most frequently reported. Eleven more deaths were reported in the update period after primary analysis; these occurred in survival follow-up and were not drug-related. Conclusions: Vismodegib is the first FDA-approved HPI; thus, long-term efficacy and safety data are particularly relevant. 18-month update data confirmed prolonged responses and consistent safety in vismodegib-treated aBCC patients. Clinical trial information: NCT00833417.

Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA4500-LBA4500 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Matt D. Galsky ◽  
Yohann Loriot ◽  
Nancy Ann Dawson ◽  
Andrea Necchi ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Attractive Alternative ◽  
Primary Analysis ◽  
Meaningful Activity ◽  
Immune Mediated ◽  
Metastatic Setting ◽  
Independent Review ◽  
Metastatic Urothelial Carcinoma ◽  
Clinical Trial Information

LBA4500 Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71% had CrCl < 60 mL/min; 13% had hearing loss ≥ 25 dB; 6% had prior PN ≥ G2; 20% had ECOG PS2. ORR was 19% (95% CI 13-28; 5% CR), and responses occurred in all IC subgroups (Table; includes DCR/PFS/OS) and in pts with poor prognostic factors. 22/23 responses were ongoing with mDOR not reached. Median follow-up was 8.5 mo (range 0.2-14.3); median tx duration was 15 wk. Atezo was generally well tolerated. Tx-related all-G and G3-4 AEs were seen in 64% and 12% of pts, respectively. Related all-G AEs ≥ 10% included fatigue, pruritus, diarrhea. 1 G5 related AE occurred (sepsis). 3% had a G3-4 immune-mediated AE. Conclusions: Atezo has clinically meaningful activity in 1L cisplatin-ineligible mUC pts, and preliminary OS is encouraging. The durable nature of response and favorable AE profile makes this an attractive alternative to chemo. NCT02108652. Clinical trial information: NCT02108652. [Table: see text]

Treatment of varicose tributaries with sclerotherapy with polidocanol 0.5 % foam

VASA ◽  
2010 ◽  
Vol 39 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Reich-Schupke ◽  
Weyer ◽  
Altmeyer ◽  
Stücker
Keyword(s):  
Scientific Evidence ◽  
Daily Practice ◽  
Severe Adverse Effect ◽  
Safe Procedure ◽  
Efficacy And Safety ◽  
Foam Sclerotherapy ◽  
History Of ◽  
One Year ◽  
Additional Therapy

Background: Although foam sclerotherapy of varicose tributaries is common in daily practice, scientific evidence for the optimal sclerosant-concentration and session-frequency is still low. This study aimed to increase the knowledge on foam sclerotherapy of varicose tributaries and to evaluate the efficacy and safety of foam sclerotherapy with 0.5 % polidocanol in tributaries with 3-6 mm in diameter. Patients and methods: Analysis of 110 legs in 76 patients. Injections were given every second or third day. A maximum of 1 injection / leg and a volume of 2ml / injection were administered per session. Controls were performed approximately 6 months and 12 months after the start of therapy. Results: 110 legs (CEAP C2-C4) were followed up for a period of 14.2 ± 4.2 months. Reflux was eliminated after 3.4 ± 2.7 injections per leg. Insufficient tributaries were detected in 23.2 % after 6.2 ± 0.9 months and in 48.2 % after 14.2 ± 4.2 months, respectively. Only 30.9 % (34 / 110) of the legs required additional therapy. In 6.4 % vein surgery was performed, in 24.5 % similar sclerotherapy was repeated. Significantly fewer sclerotherapy-sessions were required compared to the initial treatment (mean: 2.3 ± 1.4, p = 0.0054). During the whole study period thrombophlebitis (8.2 %), hyperpigmentation (14.5 %), induration in the treated region (9.1 %), pain in the treated leg (7.3 %) and migraine (0.9 %) occurred. One patient with a history of thrombosis developed thrombosis of a muscle vein (0.9 %). After one year there were just hyperpigmentation (8.2 %) and induration (1.8 %) left. No severe adverse effect occurred. Conclusions: Foam sclerotherapy with injections of 0.5 % polidocanol every 2nd or 3rd day, is a safe procedure for varicose tributaries. The evaluation of efficacy is difficult, as it can hardly be said whether the detected tributaries in the controls are recurrent veins or have recently developed in the follow-up period. The low number of retreated legs indicates a high efficacy and satisfaction of the patients.

scholarly journals Ultrasound-guided implantation of radioactive 125I seed in radioiodine refractory differentiated thyroid carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Chen ◽  
Yu kun Luo ◽  
Ying Zhang ◽  
Qing Song ◽  
Jie Tang
Keyword(s):  
Thyroid Carcinoma ◽  
Reduction Rate ◽  
Differentiated Thyroid Carcinoma ◽  
Comprehensive Treatment ◽  
Efficacy And Safety ◽  
Ultrasound Guided ◽  
Contrast Enhanced ◽  
The Us ◽  
Median Volume

Abstract Background Treatment for radioiodine refractory differentiated thyroid carcinoma (RR-DTC) is challenging. The purpose of this study was to assess the efficacy and safety of ultrasound-guided implantation of radioactive 125I-seed in radioiodine refractory differentiated thyroid carcinoma. Methods Thirty-six cervical metastatic lymph nodes (CMLNs) diagnosed with RR-DTC from 18 patients were enrolled in this retrospective study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before implantation. Follow-up comprised US, CEUS, thyroglobulin (Tg) level and routine hematology at 1–3, 6, 9 and 12 months and every 6 months thereafter. The volumes of the nodules were compared before implantation and at each follow-up point. The volume reduction rate (VRR) of nodules was also recorded. Results The median volume of the nodules was 523 mm3 (148, 2010mm3) initially, which decreased significantly to 53mm3 (0, 286mm3) (P < 0.01) at the follow-up point of 24 months with a median VRR as 95% (86,100%). During the follow-up period (the range was 24–50 months), 25 (69%) nodules had VRR greater than 90%, of which 12 (33%) nodules had VVR ≈ 100% with unclear structures and only 125I seed images were visible in the US. At the last follow-up visit, the serum Tg level decreased from 57.0 (8.6, 114.8) ng/ml to 4.9 (0.7, 50.3) ng/ml, (P < 0.01). Conclusion US-guided 125I seed implantation is safety and efficacy in treating RR- DTC. It could be an effective supplement for the comprehensive treatment of thyroid cancer.

ID: 3527213 THIRD SPACE ENDOSCOPY AFTER FORMAL ENDOSCOPY ADVANCED FELLOWSHIP TRAINING IN THE US: ONE YEAR LINEAR FOLLOW UP OF INDEPENDENT PRACTICE

2021 ◽  
Vol 93 (6) ◽  
pp. AB281
Author(s):  
Mohamed Abdelfatah Magdy ◽  
Ali M. Ahmed ◽  
Shajan Peter ◽  
Douglas R. Morgan ◽  
Qiang Cai
Keyword(s):  
Third Space ◽  
Fellowship Training ◽  
Independent Practice ◽  
The Us ◽  
One Year

Efficacy and safety of laser therapy on axillary hyperhidrosis after one year follow-up: A randomized blinded controlled trial

2015 ◽  
Vol 47 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Franck Marie Leclère ◽  
Javier Moreno-Moraga ◽  
Justo M. Alcolea ◽  
Peter M. Vogt ◽  
Josefina Royo ◽  
...  
Keyword(s):  
Laser Therapy ◽  
Controlled Trial ◽  
Efficacy And Safety ◽  
Axillary Hyperhidrosis ◽  
One Year

THU0355 Efficacy and Safety of Adalimumab in Patients with Ankylosing Spondylitis and Total Spinal Ankylosis in Croatia: One Year Follow-Up

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A285.1-A285
Author(s):  
F. Grubišić ◽  
S. Grazio ◽  
Ð. Babić-Naglić ◽  
J. Morović-Vergles ◽  
B. Anić ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Efficacy And Safety ◽  
One Year

Conditional survival nomogram after an R0 resection for gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 11-11
Author(s):  
J. L. Dikken ◽  
C. J. Van De Velde ◽  
M. Verheij ◽  
R. Baser ◽  
M. Gonen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Weight Loss ◽  
Predictive Accuracy ◽  
Performance Status ◽  
R0 Resection ◽  
Conditional Survival ◽  
Disease Free Interval ◽  
The Us ◽  
One Year

11 Background: The risk of dying of cancer is highest in the first two years after a curative resection for gastric cancer. Therefore, the prognosis of patients who did not recur in the first two years is improved because they survived this critical period, a phenomenon called conditional survival. The US-derived gastric cancer nomogram predicts disease-specific survival (DSS) based on pathological variables. However, a disease-free interval after surgery, which improves the prognosis, is not captured by the nomogram. Therefore, it has only been used directly after surgery and not in the follow-up setting. The purposes of this study were to develop a conditional survival nomogram for 1, 2 and 3-year survivors (step 1) and to test if the introduction of follow-up variables would improve predictive accuracy of the nomogram in the follow-up setting (step 2). Methods: In a combined US-Dutch population of 1642 patients who underwent an R0 resection for gastric cancer and for whom the old nomogram variables were available, a conditional survival nomogram based on the original variables was developed for one (N=1147), two (N=879) and three (N=721) year survivors (step 1). To improve predictive accuracy in the follow-up setting, weight loss, performance status (PS), hemoglobin (HGB), and albumin (ALB) at one year after resection were retrospectively collected and added to the baseline variables in a new nomogram (step 2). Results: The conditional survival nomograms for 1, 2 and 3-year survivors (step 1) showed a high predictive accuracy in the calibration plots. Surviving one, two and three years shows a median improvement of 5-year DSS of 4%, 9% and 14% respectively. The introduction of weight loss, PS, HGB, and ALB at one year after surgery (step 2) did not improve this nomogram, but availability of these variables was limited. Conclusions: A strongly predictive conditional survival nomogram was developed, giving an improved prognosis for 1, 2 and 3-year survivors of gastric cancer. Introduction of variables available at one year after resection did not further improve this nomogram. This might be caused by the limited availability of follow-up data, as well as the strong predictive accuracy of the original variables. No significant financial relationships to disclose.

Efficacy and safety of dose-dense modified TCF regimen (TCF-dd) in metastatic or locally advanced gastroesophageal cancer (GEC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4112-4112
Author(s):  
Laura Toppo ◽  
Gianluca Tomasello ◽  
Wanda Liguigli ◽  
Margherita Ratti ◽  
Rossana Poli ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Intention To Treat ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Dose Dense ◽  
Metastatic Sites ◽  
Chemotherapy Efficacy

4112 Background: TCF is a standard first line option for GEC. The Norton-Simon hypothesis suggests that chemotherapy efficacy can be enhanced by decreasing intervals between cycles. We previously reported on the high activity of TCF-dd in GEC (Tomasello 2010). The aim of this study is to investigate the efficacy and safety of this intensified dose-dense regimen in a single-center large cohort of patients (pts). Methods: 150 pts with measurable or evaluable GEC, PS 0-2, with adequate organ function, treated in our center from 2004 to 2012 received TCF-dd: Docetaxel (60-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h continuous infusion d 1-2), plus Pegfilgrastim 6 mg d 3, every 14 days. Pts aged ≥ 65 years received the same schedule with a dose reduction by 30%. Analysis was based on the intention to treat population. Results: At a median follow-up of 44 months, 128 pts were evaluable for response, all for survival. Median age 65 (range 31-81), M:F 112:38. 17 pts (11%) with locally advanced inoperable GEC, 133 pts (89%) with metastatic GEC. Metastatic sites: liver 40%, peritoneum 31%, bone 14%, lung 12%. A median of 4 cycles (range 1-7) per patient was administered. 33% required a dose reduction. 33% were treated without any delay. 10 CR, 74 PR, 24 SD and 20 PD were observed, for an ORR of 66% (95% CI 57-74). Median OS was 13 months (95% CI 9.7-14.2). Most frequent grade 3/4 toxicities: neutropenia (34%), asthenia (28%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (11%), febrile neutropenia (10%), anemia (9%), and stomatitis (4%). 11 pts (7%) [7 metastatic, 4 locally advanced] became operable after TCF-dd and underwent surgery. We identified 12 metastatic pts (8%) with overall survival > 3 years and 7 (5%) still maintaining a long lasting CR at the time of the current analysis. Conclusions: TCF-dd in GEC is very active and may be an option for conversion therapy. Toxicity can be relevant and requires a careful monitoring.

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]

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