S1063 Disease Burden in Patients With Acute Hepatic Porphyria: Experience From the Phase 3 ENVISION Study

Abstract Myelofibrosis is a hematological malignancy with a median survival of approximately 5 to 7 years. Allogeneic stem cell transplantation is the only therapeutic modality that provides a cure for myelofibrosis patients. Recently, ruxolitinib has been shown in 2 phase 3 studies to be effective in reducing splenomegaly and improving symptoms in myelofibrosis patients. Although conventional markers of disease burden (marrow histopathological features, cytogenetic and molecular markers, and reversal of cytopenias) were not uniformly improved, a survival advantage in favor of ruxolitinib therapy was demonstrated. The use of historical control cohorts to compare survival was implemented in 2 different analyses of patients enrolled in the phase 1/2 studies and has further added fuel to the controversy surrounding the significance of this survival advantage. Ruxolitinib therapy results in a dramatic reduction in circulating proinflammatory cytokine levels, which has been associated with improvement in symptoms and performance status and may provide a link to improved survival. We analyze the various data published and place in perspective the significance of the prolongation of survival associated with ruxolitinib therapy. This critical review of these data may allow physicians to more rationally assess the benefits that can be anticipated with the appropriate use of this therapy.

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Prolonged duration of response in lenvatinib responders with thyroid cancer (Russian translation)

Head and neck tumors (HNT) ◽

10.17650/2222-1468-2018-8-3-53-60 ◽

2018 ◽

Vol 8 (3) ◽

pp. 53-60

Author(s):

A. G. Gianoukakis ◽

C. E. Dutcus ◽

N. Batty ◽

M. Guo ◽

M. Baig

Keyword(s):

Thyroid Cancer ◽

Disease Burden ◽

Objective Response ◽

Progression Free Survival ◽

Primary Analysis ◽

Phase 3 ◽

Double Blind ◽

Free Survival ◽

Prolonged Duration ◽

Duration Of Response

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2 %; 95 % confidence interval (CI) 54.2–66.1) was 30.0 months (95 % CI 18.4–36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99 % CI 0.17–0.35; nominal P <0.0001). In lenvatinib responders, median PFS was 33.1 months (95 % CI 27.8–44.6) vs 7.9 months (95 % CI 5.8–10.7) in nonresponders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2 %) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders.

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Prolonged duration of response in lenvatinib responders with thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-18-0049 ◽

2018 ◽

Vol 25 (6) ◽

pp. 699-704 ◽

Cited By ~ 13

Author(s):

Andrew G Gianoukakis ◽

Corina E Dutcus ◽

Nicolas Batty ◽

Matthew Guo ◽

Mahadi Baig

Keyword(s):

Thyroid Cancer ◽

Disease Burden ◽

Objective Response ◽

Progression Free Survival ◽

Primary Analysis ◽

Phase 3 ◽

Double Blind ◽

Free Survival ◽

Prolonged Duration ◽

Duration Of Response

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2–66.1) was 30.0 months (95% CI 18.4–36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17–0.35; nominal P < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8–44.6) vs 7.9 months (95% CI 5.8–10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders.

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Reducing the Health Burden of HPV Infection Through Vaccination

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/idog/2006/83084 ◽

2006 ◽

Vol 2006 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

David Soper

Keyword(s):

Disease Burden ◽

Cervical Screening ◽

Hpv Infection ◽

Quadrivalent Vaccine ◽

Sexually Active ◽

Phase 3 ◽

Transmitted Infection ◽

Sexually Transmitted ◽

Hpv Types ◽

Vaccination Campaigns

Human papillomavirus (HPV), a sexually transmitted infection and the etiologic cause of genital warts and cervical cancer, is highly prevalent in sexually active men and women. Although cervical screening procedures have significantly reduced the disease burden associated with HPV infection, they are expensive and abnormal results cause significant emotional distress. Therefore, prevention may be an effective strategy for reducing the economic, psychosocial, and disease burden of HPV infection. Multivalent vaccines are now in clinical development. A bivalent vaccine that protects against HPV 16 and 18, and a quadrivalent vaccine which protects against HPV types 6, 11, 16, and 18, have been shown to significantly reduce the occurrence of incident and persistent HPV infections in phase 2 clinical trials; phase 3 trials are currently underway. HPV vaccines will be most effective when administered prior to initiation of sexual activity, and vaccination campaigns should aggressively target preadolescent and adolescent populations.

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MILO/ENGOT-ov11: Phase-3 Study of Binimetinib versus Physician’s Choice Chemotherapy in Recurrent or Persistent Low-grade Serous Carcinomas of the Ovary, Fallopian Tube, or Primary Peritoneum

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.06.044 ◽

2020 ◽

Vol 159 ◽

pp. 22 ◽

Cited By ~ 1

Author(s):

R.N. Grisham

Keyword(s):

Fallopian Tube ◽

Low Grade ◽

Phase 3

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Idalopirdin bei Alzheimererkrankung: nicht besser als Plazebo

Fortschritte der Neurologie · Psychiatrie ◽

10.1055/a-0570-2372 ◽

2018 ◽

Vol 86 (08) ◽

pp. 456-457

Keyword(s):

Phase 2 ◽

Phase 3 ◽

Alzheimer Demenz

Die Blockade von Serotoninrezeptoren, insbesondere des Serotonin-Rezeptortyps 5-HT6, als Zusatztherapie in Kombination mit Cholinesterasehemmer, hat in experimentellen Versuchen sowie in einer Phase-2-Studie positive Effekte bei Demenz gezeigt. Im Rahmen eines Phase-3 Entwicklungsprogramms wurde nun die Effektivität des selektiven Serotoninrezeptor-Antagonisten Idalopirdin bei leichter bis mittelschwerer Alzheimer Demenz geprüft.

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