Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5533-5533 ◽  
Author(s):  
Charlie Gourley ◽  
Michael Friedlander ◽  
Ursula A. Matulonis ◽  
Vadim Shirinkin ◽  
Frédéric Selle ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Final Analysis ◽  
Term Treatment ◽  
Tolerability Profile ◽  
Treatment Benefit ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment ◽  
Clinically Significant

5533 Background: In Study 19 (NCT00753545), a RCT in 265 pts with PSR SOC, the oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) vs placebo (PBO), with the greatest benefit seen in pts with a BRCA1/2 mutation ( BRCAm); an interim overall survival (OS) analysis suggested an advantage for olaparib-treated pts (DCO: Sep 30, 2015; Ledermann et al, 2016). We report a planned final analysis of the long-term benefit of olaparib in pts with PSR SOC in Study 19. Methods: Pts who had received ≥2 prior regimens of platinum-based chemotherapy and were in response to their most recent regimen received olaparib (400 mg bid; capsules) or PBO until disease progression. Retrospective germline or tumor testing resulted in a known BRCAm status for 254/265 pts (96%). Results: At final DCO (May 9, 2016) median OS follow-up was 78.0 months. A long-term treatment benefit and the final hazard ratio (HR) for OS vs PBO (unadjusted for crossover: 13% of PBO pts – full analysis set [FAS]; 23% of PBO pts – BRCAm subgroup) is shown (Table). Details of BRCAwt pts on treatment for ≥6 years will be presented. No new safety signals or changes in olaparib tolerability profile were seen. Conclusions: The Study 19 final analysis shows that olaparib provides clinically significant, long-term treatment benefit in pts with PSR SOC. A durable benefit was seen in ≥10% of BRCAm and BRCAwt pts, who continued to receive and benefit from olaparib for ≥6 years–unprecedented in the relapsed ovarian cancer setting. Olaparib is well tolerated in this pt population and the analysis suggests olaparib confers an OS benefit in BRCAm pts. Clinical trial information: NCT00753545. [Table: see text]

Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6002-6002 ◽  
Author(s):  
Andres Poveda ◽  
Anne Floquet ◽  
Jonathan A. Ledermann ◽  
Rebecca Asher ◽  
Richard T. Penson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment

6002 Background: SOLO2 (ENGOT ov-21; NCT01874353) showed that maintenance therapy with the PARP inhibitor olaparib in pts with platinum-sensitive relapsed ovarian cancer (PSROC) and a BRCA mutation (BRCAm) led to a statistically significant improvement in median progression-free survival (PFS) of 13.6 months vs placebo (hazard ratio [HR] 0.30). Time to second progression or death significantly improved (Pujade-Lauraine et al Lancet Oncol 2017) and a quality-adjusted PFS benefit was seen (Friedlander et al Lancet Oncol 2018) with maintenance olaparib vs placebo. We report the preplanned final OS analysis for SOLO2. Methods: Pts with PSROC and a BRCAm who had received ≥2 lines of treatment and were in response to their most recent platinum-based chemotherapy received maintenance olaparib (300 mg bid tablets) or placebo. Pts were stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6–12 months vs >12 months). OS was a secondary endpoint. The only preplanned OS sensitivity analysis was an OS analysis in the Myriad germline BRCAm subset (Myriad BRAC Analysis test). Results: At final data cut-off (Feb 3, 2020), median follow-up was 65 months in both treatment arms. A long-term treatment benefit was seen with olaparib vs placebo with an OS HR of 0.74 (95% confidence interval [CI] 0.54–1.00) in the full analysis set (FAS; unadjusted for crossover; 38.4% of placebo pts crossed over to a PARP inhibitor) (Table). At 5 years: by Kaplan-Meier estimates, 28.3% of pts in the olaparib arm vs 12.8% of pts in the placebo arm were alive and had still not received subsequent treatment; 42.1% of olaparib pts vs 33.2% of placebo pts were alive. The long-term tolerability profile of olaparib was generally consistent with that reported previously. Conclusions: In the final analysis of SOLO2, maintenance olaparib provided an unprecedented improvement of 12.9 months in median OS vs placebo. This is the first study with olaparib tablets, and the first since Study 19 (NCT00753545), to provide long-term follow-up and final OS data in pts with PSROC and a BRCAm. Clinical trial information: NCT01874353. [Table: see text]

Long-Term Treatment Results for Ovarian Tumors with Malignant Effusion in Seven Dogs

2021 ◽  
Author(s):  
Teruo Itoh ◽  
Atsuko Kojimoto ◽  
Kazuyuki Uchida ◽  
James Chambers ◽  
Hiroki Shii
Keyword(s):  
Pleural Effusion ◽  
Granulosa Cell Tumor ◽  
Postoperative Recurrence ◽  
Term Treatment ◽  
Ovarian Tumors ◽  
Malignant Effusion ◽  
Ovarian Adenocarcinoma ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment

ABSTRACT Surgery and platinum-based chemotherapy are highly efficacious for treating advanced ovarian cancers in humans, but their efficacy is less known in dogs. We evaluated the long-term treatment outcomes of seven dogs with malignant ovarian tumors with malignant abdominal effusion. Ovariohysterectomies (OVHs) were performed on all dogs; four had ovarian adenocarcinoma (AC) with gross dissemination in the peritoneum (two with pleural effusion), and three had a granulosa cell tumor (GCT) with no gross dissemination in the peritoneal cavity, although one showed pleural effusion. Effusion resolved after the OVH in all dogs. Six dogs (three ACs, three GCTs) received postoperative IV carboplatin therapy. Two dogs with GCT had no postoperative recurrence or metastasis, and one dog with GCT had recurrence 1811 days postoperatively. All dogs with AC developed recurrent effusion 171–584 days postoperatively, which resolved after intracavitary administration of cisplatin or carboplatin, with a subsequent disease-free interval of 155–368 days. Overall survival was longer for dogs with GCTs (822–1840 days) than for those with ACs (617–841 days). These results suggest that dogs with ovarian tumors with malignant effusion can survive relatively long after platinum-based chemotherapy in addition to OVH, with a more favorable prognosis for GCT than AC.

scholarly journals What does the latest meta-analysis really tell us about antidepressants?

2018 ◽  
Vol 27 (5) ◽  
pp. 430-432 ◽  
Author(s):  
J. Moncrieff
Keyword(s):  
Meta Analysis ◽  
Term Treatment ◽  
Significant Other ◽  
Brain Abnormality ◽  
Antidepressant Effects ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Chemical Imbalance

A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.

Atezolizumab (atezo) in patients with metastatic urothelial carcinoma (mUC): A 2-year clinical update from a phase Ia study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 290-290 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Thomas Powles ◽  
Joaquim Bellmunt ◽  
Fadi S. Braiteh ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Objective Response ◽  
The United States ◽  
Term Treatment ◽  
Long Term Results ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment ◽  
Previously Treated ◽  
Ecog Ps

290 Background: Atezo (anti–PD-L1) has demonstrated safety and efficacy in a broad range of cancers and is approved in the United States for mUC previously treated with platinum-based chemotherapy. Here we report long-term results in mUC from Phase Ia study NCT01375842 (PCD4989g). Methods: Previously treated mUC patients received atezo 15 mg/kg or 1200 mg IV q3w. Enrollment in this Phase Ia expansion cohort initially required PD-L1–selected status and later opened to patients regardless of PD-L1 expression on tumor-infiltrating immune cells. The primary endpoint was safety/tolerability. Secondary endpoints included investigator-assessed RECIST v1.1 ORR (confirmed), DOR and OS. Results: 95 patients were safety evaluable (Table). Median age was 66 years, 76% were male and 80% had primary bladder tumors. 61% had ECOG PS 1. 52% received ≥ 3 prior systemic therapies for mUC (70% platinum). Median treatment duration was 3 months (range: 0-32 months); 24% were treated for ≥ 1 year. Treatment-related AEs occurred in 66% (all Grade) and 8% (Grade 3-4) of patients. No treatment-related deaths were reported. In 94 objective response–evaluable patients (follow-up ≥ 12 weeks), the ORR was 27% (95% CI: 18, 37%), and the CR rate was 10%; the SD rate was 19%. mDOR was 22.1 months (95% CI: 12.1, NE months) in all patients; 56% of responses (7/9 CRs and 7/16 PRs) were ongoing at the December 15, 2015 data cutoff. With a 24-month median follow-up duration (range: 1+ to 32 months), the 1-year OS rate was 47% (95% CI: 36, 58%), and the 2-year rate was 29% (19, 40%); mOS is in the Table. Updated clinical data with further follow-up and analyses by PD-L1 status will be presented. Conclusions: Long-term treatment with atezo was well tolerated, without new safety signals in heavily pre-treated mUC patients. The durability of responses, including CRs, along with extended OS, confirm atezo as a new standard for previously treated mUC patients. Clinical trial information: NCT01375842. [Table: see text]

Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Adults With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S20) ◽  
pp. 35-43 ◽  
Author(s):  
Richard H. Weisler ◽  
Joseph Biederman ◽  
Thomas J. Spencer ◽  
Timothy E. Wilens
Keyword(s):  
Extended Release ◽  
Vital Signs ◽  
Cardiovascular Effects ◽  
Term Treatment ◽  
Healthy Adults ◽  
Hyperactivity Disorder ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Combined Subtype

AbstractObjective: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.Methods: 223 otherwise healthy adults (≥18 years of age) with ADHD combined subtype were exposed to ≤24 months of MAS XR (20–60 mg/day). Resting sitting diastolic blood pressure (DBP) and systolic blood pressur (SBP) and pulse were measured at baseline and weekly, then monthly during long-term treatment. Twelve-lead electrocardiograms were obtained at screening/baseline, weekly, then at 3-and 6-month intervals up to 24 months.Findings: With MAS XR 20–60 mg/day, mean changes in DBP (1.3±9.2 mm Hg; P=.O42), SBP (2.3±12.5 mmHg; P=.OO6), and pulse (2.1±13.4 bpm; P=.019) were small and not clinically significant. A clinically insignificant increase in QTcB (corrected by Bazett's formula) interval (7.2 msec; P<.001) was observed at 24 months. No subject exhibited QTcB interval >480 msec (QTcF [corrected by Fridericia's formula] >454 msec). Seven subjects discontinued due to a car-diovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy.Conclusion: Cardiovascular effects of long-term MAS XR (≤60 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.

Oral Butorphanol Tartrate for the Long-Term Treatment of Out-Patients with Moderate to Severe Cancer Pain

1981 ◽  
Vol 9 (2) ◽  
pp. 124-127 ◽  
Author(s):  
Jaime De La Garza
Keyword(s):  
Blood Pressure ◽  
Cancer Pain ◽  
Open Study ◽  
Analgesic Efficacy ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Oral Doses ◽  
Median Pain

The safety, tolerance and analgesic efficacy of multiple oral doses of butorphanol tartrate for the long-term treatment of cancer pain were evaluated in this open study. Thirty-five patients were treated with various doses (1 to 12 tablets per day) for 4 to 147 days. The median pain relief was fair, good, very good or excellent in 51% of the patients and poor in 49% of the patients. Global assessments were very similar. No clinically significant changes in blood pressure, weight, blood and urine chemistries were observed. Seventeen patients reported side-effects (only sedation and dry mouth) ranging from mild to severe.

Aripiprazole once monthly outpatient experience

2017 ◽  
Vol 41 (S1) ◽  
pp. S760-S760
Author(s):  
P. Sánchez Páez ◽  
J.L. Gómez Cano ◽  
L. Sánchez Flores ◽  
R. González Lucas ◽  
P. Artieda Urrutia
Keyword(s):  
Previous Treatment ◽  
Term Treatment ◽  
Tolerability Profile ◽  
Patient Profile ◽  
Co Morbidity ◽  
Long Term Treatment ◽  
Competing Interest ◽  
One Year ◽  
Image Position

IntroductionAripiprazole once monthly (AOM) is one of the most recently introduced antipsychotics with a different mechanism of action, which seems to bring clinical and tolerability implications [1].ObjectivesWe describe the patient profile that may benefit from AOM treatment.MethodsThis is a single-centre, retrospective, one year follow-up study of 13 cases of ambulatory AOM use. We analyze clinical and functional evolution, and the tolerability profile of patients in a real clinical practice basis.ResultsMean age was 53.69; 53.8% were males and 46.2% females. The most frequent diagnosis was Schizophrenia and other chronic psychosis (69.3%). Only 7.7% had co-morbidity with substance use disorder (cocaine); 61.6% were on previous treatment with other injectable anti-psychotics; 84,6% of the sample received AOM as monotherapy. Reasons for switching to AOM are shown on Fig. 1. Events during switching are shown on Fig. 2. Outcomes with AOM long-term treatment were positive in 84.61% of cases and are shown on Fig. 3.ConclusionsSwitching to AOM could be considered as a good strategy to improve tolerability, functionality and ultimately adherence to treatment in patients in middle age of life with a chronic psychotic disorder [2].Fig. 1Reasons for switching.Fig. 2Events during switching.Fig. 3Outcomes with AOM.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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