Two or more dexamethasone intravitreal implants in treatment-naïve patients with macular edema due to retinal vein occlusion: subgroup analysis of a retrospective chart review study

BACKGROUND: Dexamethasone intravitreal implant (DEX implant) is a biodegradable, sustained-release implant that releases dexamethasone for up to 6 months. We evaluated the efficacy and safety of DEX implant in the treatment of macular edema secondary to retinal vein occlusion (RVO) in treatment-naïve patients. METHODS: A multicenter, retrospective, open-label chart review study investigated the efficacy and safety of DEX implant treatment in 289 patients with macular edema secondary to branch or central RVO (BRVO, CRVO) who received ≥2 treatments with DEX implant in the study eye. Concomitant adjunctive RVO treatments were permitted. Data collected from the time of the first implant (baseline) to 3–6 months after the last implant included best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography. In this subgroup analysis, we evaluated outcomes in patients who had received no previous treatment for RVO complications. RESULTS: Thirty-nine patients were treatment-naïve at the time of their first DEX implant (18 BRVO, 21 CRVO). Before the initial DEX implant, the mean duration of macular edema in treatment-naïve patients was 4.9 months, mean central retinal thickness was 550 μm, and mean Early Treatment Diabetic Retinopathy Study BCVA was 8.5 lines (20/125 Snellen). Treatment-naïve patients received a mean of 2.9 implants, either as monotherapy (n = 12) or with adjunctive RVO treatments (n = 27). The mean interval between implants was 177 days. After the first through sixth implants, mean changes from baseline BCVA ranged from +3.0 − +8.0 lines, and mean decreases from baseline central retinal thickness ranged from 241–459 μm. BCVA improved in both BRVO and CRVO and in both phakic and pseudophakic eyes. Overall, 83.8 % of treatment-naïve patients gained ≥2 lines in BCVA, 70.3 % gained ≥3 lines in BCVA, and 56.4 % achieved central retinal thickness ≤250 μm. The most common adverse event was increased intraocular pressure. Fifteen treatment-naïve patients had intraocular pressure ≥25 mm Hg; none required laser or incisional glaucoma surgery. CONCLUSION: Treatment with 2 or more DEX implants had a favorable safety profile and improved visual acuity and anatomic outcomes when used, either alone or with adjunctive RVO therapy, as initial treatment for RVO-associated macular edema. TRIAL REGISTRATION: ClinicalTrials.gov NCT01411696, registered on August 5, 2011

Abstract OT3-03-02: Maximising recruitment and retention of patients into UK-ANZ POSNOC trial

Abstract The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Surgeons want to gather robust evidence but may experience considerable discomfort in relation to their clinical instincts and concerns about patient eligibility and safety. The ongoing POSNOC study design is pragmatic to maximise recruitment. A patient information DVD is used as an adjunct to patient information leaflet. The protocol allows for either axillary radiotherapy or axillary node clearance. Here we report recruitment and retention of participants into POSNOC, the associated barriers and challenges, and various strategies employed to overcome these barriers. A total of 368 participants were recruited till May 2016. A total of 90%(331) of participants were recruited via non intra-operative pathway, and 10%(37) from intra-operative pathway. The most common known reasons for non-participation of eligible women were - woman wanting axillary treatment and clinician/MDT deciding woman needs axillary treatment. The mean randomisation yield from screening was 30% (range 6 to 100%). The highest recruiting sites were Derby, Manchester, Oxford, Belfast and Bristol. The screening logs identified barriers as: fewer than estimated eligible women, clinicians not offering trial to all eligible patients and patient acceptability. To reach recruitment targets in a timely fashion, a multifaceted approach is being employed. a) Protocol amendments to widen the inclusion criteria, b) 250 patients to be recruited by Australia and New Zealand sites, c) additional 50 sites to be opened in the UK, d) encourage OSNA centres to follow the non intra-operative pathway, e) communication workshops, f) POSNOC poster in breast units to raise awareness, g) questionnaire survey - sites to identify local issues and their perceptions about recruitment, h) social media - POSNOC WhatsApp group i) newsletters and briefings, j) competitions, k) tips to maximise recruitment document that includes a template script of one way to introduce the study l) regional telephone conferences for research nurses, m) investigator meeting. The success of these strategies remains to be assessed and shall be reported separately. Citation Format: Goyal A, Coleman RE, Dodwell D, Fallowfield L, Jenkins VA, Mann B, Reed MW, POSNOC Trial Management Group. Maximising recruitment and retention of patients into UK-ANZ POSNOC trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-03-02.</jats:p

19. Commission de la Variation des Latitudes

The values given below are those published in every annual report of the international latitude work. Those for the first three years were calculated from the observed results in three stations, namely, Mizusawa, Carloforte and Ukiah, while that for the last year was from the results of four stations with one additional station, Kitab.</jats:p

8. Commission de l’Astronomie Méridienne

Since the last meeting of the International Astronomical Union, much attention has been given both in Germany and America to the systematic errors of the fundamental catalogues of Boss and Auwers. This is of special importance if the proper motions of any of the stars are to be used in the verification of the rotation in the plane of the Milky Way. The periodic errors in the proper motions, both in right ascension and declination, are of significance in this connection, while the motion of the equinox is required for the determination of precession, and the systematic correction to the proper motions of declination affects the position of the Solar Apex and the Vertices of the Star Streams.</jats:p

19. Commission de la Variation des Latitudes

The values given below are those published in each annual report of the international latitude work. They were calculated from the observations at five stations, except the last part of 1934 which was made without Kitab, because the observation books from Kitab since November 1934 have arrived too late at the Central Bureau.</jats:p

Adjuvant therapy with zoledronic acid (AZURE-BIG 01/04): The influence of menopausal status and age on treatment effects.

502 Background: The AZURE trial evaluated the use of zoledronic acid (ZOL) in addition to standard adjuvant therapy in patients with stage II/III breast cancer. Although analysis of the primary endpoint in the total study population showed no significant effects on disease outcomes, pre-specified subgroup analyses identified significant benefit in both invasive disease-free survival (IDFS) and overall survival (OS) in women &gt;5years postmenopause (Coleman et al. NESM. 2011;365:1396–1405). Here we evaluate the treatment modifying effects of both menopausal status and age. Methods: 3360 patients were randomized to receive standard (neo) adjuvant systemic therapy +/- ZOL 4mg iv every 3-4 weeks for 6 doses, then at reduced frequency to complete 5 years treatment. Results: ZOL had no overall effect on IDFS or OS at a median follow-up of 59 months. Pre-specified subgroup analyses showed significant heterogeneity of treatment effect (chi21 =7.91; p=.0049) on IDFS between those who were &gt;5 years post-menopause (n=1041; adjusted HR= 0.75; 95% CI 0.59-0.96, p=0.02) and all other (pre, peri and unknown status) menopausal groups (n=2318; adjusted HR= 1.15; 95% CI 0.97-1.36, p=0.11). The treatment interaction between the two menopausal groups was related to differences in first extra-skeletal IDFS events (chi21 = 14.00, p=0.0002), rather than first recurrence in bone (chi21 = 0.14, p=0.70). In women aged &lt;40, a significant worsening in extra-skeletal IDFS events was seen (HR = 1.68; 95% CI = 1.14-2.47, p=.008). Although the ZOL effect on IDFS improved by age from a negative effect in younger patients (&lt;40) to a beneficial effect for those aged 54 and over (chi21(trend) = 5.96, p=0.015, using Cox model analysis to test for an interaction effect between age, menopausal status and treatment for IDFS (using age 55 as a cut-off) showed that the age effect is reversed by menopausal status, with this model providing a significantly better fit (chi22 = 22.8, p=.00001) than the aforementioned linear model. Conclusions: These results suggest menopausal status is more informative than age in the selection of patients for treatment with ZOL. In women aged &lt;40, ZOL may increase extra-skeletal recurrence. </jats:p

19. Commission de la Variation des Latitudes

In consequence of the decision made by the Fifth General Assembly of the I.A.U. I have been entrusted, from January 1936, with the direction of the Central Bureau for the International Service of Latitudes.I am much indebted to Prof. Kimura, who preceded me as Director and to Prof. Kohlschütter, Director of the Geodetic Institute of Potsdam, for information and advice, which has been of great assistance to me; therefore I desire to acknowledge to them my deep gratitude.</jats:p

Abstract P2-14-01: Fulvestrant vs exemestane for treatment of metastatic breast cancer in patients with acquired resistance to non-steroidal aromatase inhibitors – a meta-analysis of EFECT and SoFEA (CRUKE/03/021 &amp; CRUK/09/007)

Abstract Background: Optimal endocrine treatment (trt) for post-menopausal women with ER+ advanced breast cancer (ABC) progressing on or following a non-steroidal (NS) aromatase inhibitor (AI) is unclear. The EFECT study showed no difference in efficacy between the steroidal antiestrogen fulvestrant (F) &amp; steroidal AI exemestane (E) in this setting (HR = 0.96, 95%CI: 0.82, 1.13; p = 0.65). Pre-clinical data suggest F may be more effective in a low estrogen environment. SoFEA investigated F combined with anastrozole (F+A) in patients (pts) with acquired resistance to previous AI compared with F alone &amp; F alone vs. E. The combination of F+A was no better than F (HR = 1.00, 95%CI: 0.83, 1.21; p = 0.98) nor F alone better than E (HR = 0.95, 95%CI: 0.79, 1.14; p = 0.56); the lack of added benefit for F+A is consistent with previous 1st-line studies that have assessed this combination versus A alone (FACT &amp; SWOG-S0226). Methods: SoFEA is a multi-center partially blinded randomized phase III study postmenopausal women were allocated to F plus A (F+A n=243), F plus placebo (n = 231) or E (n = 249). Similarly, EFECT is a randomized, double-blind, placebo controlled, multi-center phase III trial of F (n = 351) versus E (n = 342) in postmenopausal women (see table). However, given the differences in prior endocrine therapy/responsiveness within SoFEA &amp; EFECT populations, an individual pt meta-analysis combining data from SoFEA &amp; EFECT will be conducted enabling exploration of putative effects within specific pt subgroups to establish evidence in support, or not, of a pt subgroup sensitive to F at the dose used in these trials. Subgroups to be analysed include receptor status, visceral involvement, AI sensitivity, age, NSAI setting &amp; time on NSAI. Results: 723 pts (480 in F &amp; E) were enrolled from 82 UK &amp; 4 South Korean centers (03/2004-04/2010) in SoFEA. 693 pts were enrolled from 138 centers worldwide (08/2003-11/2005) in EFECT. Trt was well tolerated in both trials; serious adverse events were rare. The meta-analysis will be conducted in July 2012 &amp; results presented. Conclusion: Combining individual pt data from SoFEA &amp; EFECT via meta-analysis will provide definitive clinical information on pt's response to F at the dose used in these studies, in particular whether certain pts with acquired resistance to NSAI do experience benefit of use of this antiestrogen as opposed to E. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-01.</jats:p