Maintenance Treatment Of Patients Research Articles

Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring

Objective Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM). Methods Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch. Primary outcome was proportion of patients on SC treatment after 26 weeks. Secondary outcomes included adverse events (AEs), clinical disease activity, biochemical markers, treatment interval, serum-VDZ (s-VDZ), preferred route of administration and health-related quality of life. Results In total, 108 patients were switched. After 26 weeks, 100 patients (92.6%) were still on SC treatment and median s-VDZ was 47.6 mg/L (IQR 41.3 − 54.6). The most frequent AE was injection site reaction (ISR), reported by 20 patients (18.5%). There were no clinically significant changes in disease activity, biochemical markers and quality of life. The proportion of patients preferring SC administration increased from 28.0% before switch to 59.4% after 26 weeks (p < 0.001). Conclusions Nine out of ten patients still received SC treatment after 26 weeks. No change in disease activity occurred, and levels of serum VDZ increased. Although almost one fifth of patients experienced ISRs, a higher proportion favored SC administration at 26 weeks. This study demonstrates that SC maintenance treatment is a safe and feasible alternative to IV treatment.

Abstract P3-02-04: Phase II study of Pembrolizumab Maintenance treatment in patients with HER2-negative inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) after response to chemotherapy

Abstract Accumulating physical and hematologic toxicities make the indefinite use of chemotherapy unfeasible for many patients with metastatic/recurrent HER2– IBC or TNBC. Whether maintenance immunotherapy has a role in the treatment of these patients is unclear. We conducted a single-arm phase II trial of pembrolizumab monotherapy in patients with metastatic/recurrent HER2– IBC or TNBC (regardless of their PD-L1 expression status) and report here the clinical data from this trial. Methods: Eligible patients were enrolled between 2015 and 2022 and had had a CR, a PR, or SD after a minimum of 3 cycles of chemotherapy for metastatic/recurrent disease. PD-L1 expression status was not used to determine eligibility. Patients received 200 mg of pembrolizumab every 3 weeks (q3w) until disease progression, intolerable toxicity, or 2 years. In late 2021, the study was amended to allow patients who had received ≥8 cycles of q3w therapy to transition to q6w dosing (400 mg), based on the FDA’s approval of both dosing regimens across all indications. The primary endpoint was the 4-month disease control rate (DCR); exploratory endpoints included safety and correlative biomarkers from tissue and blood to ascertain associations between clinical response and PD-L1 expression, T-cell clonality, and immune profiling. Results: Of 43 patients (median age, 54 years; range, 34-77 years), 11 had IBC (10 with triple-negative IBC and 1 with ER+ HER2– IBC), and 32 had TNBC. The 4-month DCR was 58.1% (95% CI: 43.4%-72.9%). During a median follow-up of 11.4 months, 25 patients died. The entire cohort’s median OS and PFS times were 26.0 months (95% CI: 11.0-33.5 months) and 4.8 months (95% CI: 3.0-7.1 months), respectively. The median OS times of the IBC and TNBC groups did not differ significantly, nor did those of the CR, PR, and SD groups. The median PFS times of the IBC group (2.2 months) and TNBC group (4.8 months) did not differ significantly (p = .12), but those of the CR, PR, and SD groups did (not reached, 10.3 months, and 3.4 months, respectively; p = .01). Among the 37 patients who are off study treatment, most patients (84%; n=31/37) discontinued treatment owing to disease progression rather than toxicities (n=2), and the toxicities overall were consistent with the known profile of single-agent anti-PD1. Five patients had grade 3 events; there were no grade 4 or 5 events. Three patients had irreversible endocrinopathies (thyroiditis and adrenal insufficiency) requiring hormone replacement, but only 1 patient discontinued pembrolizumab because of these events. One patient discontinued treatment because of optic neuritis requiring steroids. Four patients completed 2 years of treatment without disease progression. Conclusions: Pembrolizumab maintenance therapy achieves acceptable disease control after induction chemotherapy. The PFS in this trial compares favorably to the expected durations of response to later lines of therapy. The toxicity profile of pembrolizumab compares favorably with those of chemotherapy and ADCs, which may provide a rationale for the use of ICIs in this setting. However, whether pembrolizumab maintenance therapy is helpful in TNBC patients who have received concurrent pembrolizumab with neoadjuvant chemotherapy is unknown, as these patients were excluded from the trial. Acknowledgements: This trial was supported by Merck. Citation Format: Toshiaki Iwase, Angela Alexander, Vivian Chiv, Megumi Kai, Kumiko Kida, Charla Parker, Angela N. Marx, Evan Cohen, Hui Gao, James Reuben, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, David Ramirez, Debu Tripathy, Daniel Booser, Clinton Yam, Vicente Valero, Bora Lim, Naoto T. Ueno, Jie S. Willey. Phase II study of Pembrolizumab Maintenance treatment in patients with HER2-negative inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) after response to chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-04.

Use of paliperidone palmitate half-yearly release in patients diagnosed with psychotic disorder: profile and satisfaction of use

IntroductionThe lack of insight can be present among patients with a diagnosis of schizophrenia, which often results in lack of adherence to pharmacological treatments1 and, subsequently, in treatment discontinuation and relapses2. This vicious pattern leads to further clinical deterioration, impaired functioning, and reduced quality of life 3. There is a plethora of evidence supporting the fact that long-acting injectable and depot antipsychotics can increase adherence to treatment, reduce the risk of discontinuation and hospital admissions4. It is also known that low fluctuations between peaks and lows in plasma drug levels could be related to a better tolerability profiles5. A new paliperidone palmitate prolonged release formulation, which is administered twice annually, has been approved as maintenance treatment for patients with schizophrenia who are already stable on the monthly or quarterly prolonged release paliperidone palmitate6.ObjectivesWe aimed to evaluate the transition of monthly and quarterly paliperidone palmitate to the new six-monthly formulation and patients’ satisfaction with it in a real-world clinical setting.MethodsWe collected a basic epidemiologic questionnaire, responses to a query about local pain after administration, and the Drugs Attitude Inventory (DAI).ResultsA total of 21 patients from an outpatient clinic for severe mental disorders with a long evolution of their disease in Salamanca, Spain, were included. All of them had a DSM5-TR diagnosis of Schizophrenia. Sixteen were male and 5 female. The mean age was 42.6 years. 14 were receiving quartlery paliperidone palmitate (10 with high doses (525 mg) and 4 with moderate doses (350 mg)) and 7 were on monthly injections (6 with high doses (150 mg) and 1 with a moderate dose (100 mg)). Those receiving moderate doses of quarterly or monthly paliperidone palmitate were administered 700 mg of six-monthly paliperidone palmitate; 1000 mg were injected to those with higher doses. The mean score on the DAI scale was 8. Only one patient reported an increase in local pain after the injection, and another reported dissatisfaction with the administration in the gluteus instead of the deltoid muscle. The first administration of the new formulation in our site was on June 26th; to date none of these patients have required hospital admission due to relapse.ConclusionsSix-monthly prolonged release paliperidone palmitate seems to be an effective maintenance treatment for schizophrenia. In addition, this new formulation is well received and tolerated by patients previously on monthly or quarterly formulations of the same drug.Disclosure of InterestNone Declared

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Full analysis from AVENANCE: A real-world study of avelumab first-line (1L) maintenance treatment in patients (pts) with advanced urothelial carcinoma (aUC).

471 Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (CTx). The JAVELIN Bladder regimen is now standard of care with level 1 evidence in international treatment guidelines. The AVENANCE study (NCT04822350), is investigating the efficacy and safety of avelumab 1L maintenance in a real-world population of pts with aUC in France. Data from the full analysis set are reported for the first time. Methods: In this ongoing, noninterventional, ambispective study, eligible pts have locally advanced or metastatic UC that has not progressed with 1L platinum-based CTx and previous, ongoing, or planned avelumab 1L maintenance treatment. The primary endpoint is OS from start of avelumab; secondary endpoints include progression-free survival (PFS), duration of treatment (DOT), and safety. Results: 591 pts received avelumab. At data cutoff (July 31, 2022), median follow-up was 12.0 mo (95% CI, 10.9-12.9). Median age was 73.1 y (IQR, 67.0-78.1). At start of 1L CTx (excluding pts with missing data), disease stage was metastatic in 524 pts (90.5%; visceral metastases in 426 [81.5%]) and locally advanced in 54 (9.3%). ECOG PS was 0-1 in 407 pts (85.3%) and 2-3 in 69 (14.5%). Tumor histology was pure UC in 528 pts (91.8%) and UC with variant or pure variant in 47 (8.2%). 1L CTx was gemcitabine + carboplatin (GemCarbo), gemcitabine + cisplatin (GemCis), dose-dense methotrexate + vinblastine + adriamycin + cisplatin (DD-MVAC), and other in 353 (61.0%), 170 (29.4%), 28 (4.8%), and 28 (4.8%) pts, respectively. Median number of cycles was 5 (range, 1-10). Median DOT with avelumab was 5.8 mo (95% CI, 5.2-7.0); 241 pts (40.8%) remained on treatment at data cutoff. The most common reasons for treatment discontinuation were disease progression (74.1% [n=258]), death (11.5% [n=40]), and adverse events ([AEs] 10.3% [n=36]). Median OS from start of avelumab was 18.4 mo (95% CI, 15.4-not estimable [NE]), the 12-month OS rate was 64.8% (95% CI, 60.0%-69.1%), and median PFS was 5.7 mo (95% CI, 5.3-7.0). In pts who had received GemCarbo, GemCis, or DD-MVAC, median OS (95% CI) was 16.2 mo (13.4-NE), not reached (NR; 18.1-NE), and NR (15.2-NE), respectively. Subgroups analyses will be presented. 218 pts received subsequent 2L, including CTx, antibody-drug conjugates, immunotherapy, and other in 186 (85.3%), 22 (10.1%), 6 (2.8%), and 4 (1.8%) pts, respectively. Any-grade treatment-related AEs (TRAEs) occurred in 217 pts (36.7%), including serious TRAEs in 29 (4.9%). Conclusions: Real-world data for avelumab 1L maintenance in pts with aUC from AVENANCE support the findings of JAVELIN Bladder 100 and confirm the clinical activity and acceptable safety profile of avelumab in a heterogeneous population. Clinical trial information: NCT04822350 .

P786 Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved clinical outcomes in patients with Crohn’s disease

Abstract Background STRIDE-II guidelines recommend endoscopic healing as an important treatment goal in Crohn’s disease (CD). This study evaluated the association of achieving endoscopic outcomes at week 12 and clinical outcomes at week 52 of maintenance treatment in patients with CD treated with upadacitinib (UPA). Methods This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and the maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Clinical outcomes (CD activity index [CDAI] remission, CDAI response, steroid-free CDAI remission, high sensitivity C-reactive protein [hs-CRP] level ≤5 mg/L, and fecal calprotectin level [F-cal] ≤250 mcg/g), were evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test. Results Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.3%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained clinical outcomes at week 52 (CDAI remission, 52.0% vs 34.6%; CDAI response, 54.6% vs 39.5%; hsCRP ≤5 mg/L, 52.0% vs 30.8%; and F-cal ≤250 mcg/g, 42.1% vs 21.6%; P≤0.01, Table 1). Patients who achieved an endoscopic response vs those who did not at end of induction were also more likely to attain steroid-free CDAI remission (50.0% vs 30.9%) at week 52, (P≤0.05, Table 1). Similar findings were observed in patients who achieved endoscopic remission vs those who did not at end of induction (P≤0.01, Table 1). Significantly more patients attained CDAI remission (58.7% vs 37.7%), CDAI response (58.7% vs 42.7%), hsCRP ≤5 mg/L (58.7% vs 35.0%) and F-cal ≤250 mcg/g (50.7% vs 25.0%) at week 52, among patients who achieved ulcer-free endoscopy vs those who did not at end of induction (P≤0.05, Table 1). Conclusion Achieving endoscopic outcomes at end of induction is associated with meaningful improvement in symptoms and inflammatory biomarkers at 52 weeks for patients with CD receiving UPA therapy. Endoscopic remission and ulcer-free endoscopy are associated with very similar long-term benefits.

P585 Duration of response to ozanimod after treatment withdrawal: results from the phase 3 True North study

Abstract Background The phase 3 True North randomised trial demonstrated the efficacy and safety of ozanimod (OZA) in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to loss of OZA response in patients who discontinued OZA and switched to placebo (PBO) in the True North maintenance period (MP). Methods In True North, patients were randomised to once-daily oral OZA 0.92 mg or PBO or to open-label OZA during a 10-week induction period (IP). Patients with clinical response to OZA at Week 10 were rerandomised to OZA (OZA/OZA) or PBO (OZA/PBO) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points vs Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in OZA/OZA and OZA/PBO patients who entered the MP after achieving clinical remission (CRM) or clinical response (CRS only, excluding patients in CRM) at Week 10. Results In the True North MP, 230 patients continued OZA (CRM, n=82; CRS only, n=148) and 227 patients switched to PBO (CRM, n=79; CRS only, n=148). Baseline characteristics were generally similar between groups. Patients in CRS only at Week 10 had a numerically higher proportion with severe disease and prior immunosuppressive medication use vs CRM patients (Table). Differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of OZA/OZA patients were without relapse vs OZA/PBO patients (Figure). MP Week 42 Kaplan-Meier estimates of no relapse were 86.1% and 62.6% for OZA/OZA and OZA/PBO patients, respectively. Additionally, patients in CRM at Week 10 had higher rates of nonrelapse during the MP vs those in CRS only at MP entry. Kaplan-Meier estimates of nonrelapse at MP Week 42 were 67.9% and 59.7% in OZA/PBO patients with CRM and CRS, respectively, and 90.9% and 83.4% in OZA/OZA patients with CRM and CRS, respectively. Conclusion This analysis shows that OZA is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieve clinical response at Week 10. These data show that OZA maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.

P548 Efficacy outcomes of placebo maintenance treatment in patients with moderate to severe Crohn’s disease who responded to placebo induction therapy: Post-hoc analysis of the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Risankizumab Studies

Abstract Background In the risankizumab (RZB) phase 3 clinical programme, Crohn’s disease (CD) patients who responded to RZB intravenous (IV) induction were re-randomised to RZB or placebo (PBO) (withdrawal PBO subcutaneous [SC] in maintenance (FORTIFY), while responders to PBO induction continued receiving PBO. Patients in the withdrawal (PBO SC) arm of FORTIFY who received IV RZB induction achieved high rates of clinical response/remission at Week (Wk) 52 likely due to the prolonged PK/PD effect of RZB and robust efficacy during induction.1 Here, we describe disease activity outcomes in non-randomised patients who received PBO during both induction and maintenance. Methods: This post-hoc analysis included patients who received PBO IV in the induction study (ADVANCE or MOTIVATE), achieved clinical response (definition in Figure footnote) at Wk 12, and continued on PBO SC during FORTIFY.1,2 Subjective measures of disease activity (clinical remission [per CD Activity Index (CDAI)] and per stool frequency [SF] and abdominal pain score [APS], CDAI clinical response, and SF/APS enhanced clinical response), as well as objective measures of biomarkers (high sensitivity C-Reactive Protein and faecal calprotectin) levels and endoscopic outcomes (response, remission, and ulcer-free endoscopy), during FORTIFY were evaluated (endpoint definitions in Figure footnotes) at Wk 52. Biomarkers were additionally evaluated at induction baseline. For reference only, previously reported data from patients who were clinical responders to RZB IV induction and were re-randomised in FORTIFY are presented alongside data from the continuous PBO patients subgroup.1,2 Results In the 104 patients who received PBO during both induction and maintenance, clinical response and remission rates decreased steadily during FORTIFY (Figure), while biomarker levels were relatively unchanged from induction baseline to FORTIFY Wk 52. In contrast, a slower rate of loss of response per clinical response/remission and lower biomarker levels over time were observed in RZB IV induction responders re-randomised to PBO in FORTIFY. Although already low, endoscopic response rates in the continuous PBO group decreased from FORTIFY Wk 0 to Wk 52, whereas endoscopic remission and ulcer-free endoscopy rates remained unchanged. Conclusion The symptomatic improvement achieved in patients clinically responding to PBO during induction was not maintained with continued PBO treatment in maintenance, unlike that observed in patients withdrawn from RZB, underscoring the durability of RZB induction response.1 Most objective measures of disease activity in patients receiving continuous PBO were relatively unchanged over time, with biomarkers remaining elevated and endoscopic rates of response low.

288 Once-daily crisaborole as a long-term maintenance treatment in patients with mild-to-moderate atopic dermatitis: A 52-week clinical trial

Abstract Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control despite patient adherence, with safety concerns limiting the long-term use of many therapies. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. Crisaborole has the potential as a long-term maintenance therapy. To assess the long-term efficacy and safety of crisaborole once daily as a maintenance treatment to reduce the incidence of flares in patients who had achieved response with treatment with crisaborole twice daily. CrisADe CONTROL (NCT04040192) was a randomized, double-blind, vehicle-controlled, 52-week, phase 3 study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. In an open-label run-in period, patients received crisaborole twice daily for up to 8 weeks. Patients who achieved success per Investigator’s Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement from baseline) and ≥ 50% reduction from baseline on the Eczema Area and Severity Index during the run-in were randomly assigned to receive blinded crisaborole or vehicle once daily during the 52-week maintenance period. Patients who experienced a flare (ISGA score ≥2) during the maintenance period switched to crisaborole twice daily for up to 12 weeks (assessed every 4 weeks); if the flare resolved (ISGA score ≤ 1), patients resumed their blinded once-daily treatment. Endpoints included flare-free maintenance until the onset of the first flare (primary), the number of days without flare and the number of flares. The incidence of treatment-emergent adverse events was also evaluated. Of 270 randomly assigned patients, 135 were assigned to crisaborole and 135 to a vehicle once daily. The median time of flare-free maintenance was longer for patients treated with crisaborole vs. vehicle (111 vs. 30 days, respectively; P = 0.0034). The mean number of flare-free days was higher for patients treated with crisaborole vs. vehicle (234.0 vs. 199.4, respectively; P = 0.0346). The mean number of flares was lower for patients treated with crisaborole vs. vehicle (0.95 vs. 1.36, respectively; P = 0.0042). Crisaborole was well tolerated, with no unexpected safety findings or new safety signals when used as a maintenance treatment for 52 weeks. Once-daily treatment with crisaborole was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and paediatric patients with mild-to-moderate AD.

Intravenous ustekinumab maintenance treatment in patients with loss of response to subcutaneous dosing.

Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST. We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST. The clinical response and remission was analyzed at week 12, defined as either Harvey-Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed. We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study. IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.

The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma - A targeted literature review.

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.

Characteristics of initiators of budesonide/glycopyrrolate/formoterol for treatment of chronic obstructive pulmonary disease (COPD) in the United States: the AURA study.

A twice-daily single inhaler triple therapy consisting of budesonide/glycopyrrolate/formoterol fumarate (BGF) was approved by the US Food and Drug Administration (FDA) in July 2020 as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The objective of this AURA study is to describe patient characteristics, exacerbation and treatment history, and healthcare resource utilization (HCRU) before BGF initiation to better inform treatment decisions for prescribers. This retrospective cohort study leveraged data of all payer types from IQVIA's Longitudinal Prescription Data (LRx) linked to Medical Data (Dx). Patients with COPD who had ⩾1 LRx claim for BGF between 1 October 2020 and 30 September 2021 were included. The date of first BGF claim was the index date. Patient demographic and clinical characteristics, history of COPD exacerbation or related event, treatment history, and HCRU were assessed during the 12 months before index (baseline). We identified 30,339 patients with COPD initiating BGF (mean age: 68.2 years; 57.1% female; 67.6% Medicare). Unspecified COPD (J44.9; 74.0%) was the most commonly coded COPD phenotype. The most prevalent respiratory conditions/symptoms were dyspnea (50.8%), lower respiratory tract infection (25.3%), and sleep apnea (19.0%). Uncomplicated hypertension (58.8%), dyslipidemia (43.9%), cardiovascular disease (41.4%), and heart failure (19.9%) were the most prevalent nonrespiratory conditions. During the 12-month baseline, 57.9% of patients had evidence of a COPD exacerbation or related event, and 14.9% had ⩾1 COPD-related emergency department (ED) visit; 21.0% of patients had evidence of prior triple therapy use, while 54.3% had ⩾1 oral corticosteroid (OCS) fill. Among OCS users, 29.9% had cumulative exposures >1000 mg [median [Q1-Q3] exposure: 520 (260-1183) mg]. This real-world data analysis indicates that BGF is being initiated in patients with COPD experiencing symptoms and exacerbations despite current therapy, and among patients who have various chronic comorbidities, most often cardiopulmonary-related.

EE602 Budget Impact Analysis of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate for COPD in the Italian Healthcare System

Budesonide/glycopyrronium/formoterol fumarate dihydrate 320/14.4/10 μg (BGF) triple therapy is approved as maintenance treatment in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) in the European Union. In a published network meta-analysis (Bourdin et al. Adv Ther 2021:38;3089–3112), BGF demonstrated comparable efficacy to other fixed-dose combination therapies and open-triple combinations in terms of exacerbation rate reductions. This study aimed to evaluate the cost impact of BGF entry on the Italian healthcare system for managing this patient population.

EE432 Budget Impact Analysis of Avelumab + Best Supportive Care (BSC) as First-Line Maintenance Treatment in Patients With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) in Ireland

EE432 Budget Impact Analysis of Avelumab + Best Supportive Care (BSC) as First-Line Maintenance Treatment in Patients With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) in Ireland

S14 Duration of Response After Ozanimod Withdrawal: Phase 3 True North Study Results

Background: The phase 3 True North (TN) randomized trial demonstrated efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to disease relapse in patients who discontinued ozanimod and switched to placebo in the TN maintenance period (MP). Methods: In TN, patients were randomized to once-daily oral ozanimod 0.92 mg or placebo or to open-label ozanimod during a 10-week induction period (IP). Patients with clinical response to ozanimod at Week 10 were rerandomized to ozanimod (continuous ozanimod) or placebo (ozanimod/placebo) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points versus Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in continuous ozanimod and ozanimod/placebo patients who entered the MP after achieving clinical remission or clinical response only (excluding patients in clinical remission) at Week 10. Results: In the TN MP, 230 patients continued ozanimod (clinical remission, n = 82; clinical response only, n = 148) and 227 patients switched to placebo (clinical remission, n = 79; clinical response only, n = 148). Baseline characteristics were generally similar between groups, except the group achieving clinical remission had less severe disease at baseline and fewer patients had a history of other prior immunosuppressive medication use than the group achieving clinical response only. Endoscopic disease severity improved from baseline, with all patients in clinical remission and 15.5% in clinical response achieving an endoscopic score of 0 or 1 at Week 10 (ie, MP entry). In the overall MP population, differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of patients on continuous ozanimod were without relapse versus those who switched to placebo. Kaplan-Meier (KM) estimates of no relapse at MP Week 42 were 86.1% for continuous ozanimod and 62.6% for ozanimod/placebo groups. Additionally, patients in clinical remission at Week 10 had higher rates of nonrelapse during the MP versus those in clinical response only at MP entry. KM estimates of nonrelapse at MP Week 42 were 90.9% for patients on continuous ozanimod and 67.9% for patients in the ozanimod/placebo group who achieved clinical remission, and 83.4% and 59.7% in the continuous ozanimod and ozanimod/placebo groups with clinical response only, respectively. Conclusion(s): This analysis shows that ozanimod is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieved clinical response at Week 10. These data show that ozanimod maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.

178O Rucaparib maintenance treatment in patients (pts) with newly diagnosed ovarian cancer (OC): Defining benefit according to disease risk subgroups within the phase III ATHENA–MONO study

In ATHENA–MONO (GOG-3020/ENGOT-ov45; NCT03522246), progression-free survival (PFS) improvement was observed with first-line (1L) rucaparib maintenance treatment vs placebo in pts with advanced OC, regardless of molecular characteristics (median PFS, 20.2 vs 9.2 months, log-rank P<.0001; HR, 0.52; 95% CI, 0.40–0.68). Pts with or without high-risk clinical characteristics for disease progression were enrolled in ATHENA–MONO. In the subgroup analyses presented here, we sought to evaluate if all pts benefited from rucaparib 1L maintenance treatment, including those with more favourable prognostic factors at baseline.

TRAIL Receptor Targeting Agents Potentiate PARP Inhibitor Efficacy in Pancreatic Cancer Independently of BRCA2 Mutation Status.

Chemotherapy, the standard treatment for pancreatic ductal adenocarcinoma (PDAC), has only a modest effect on the outcome of patients with late-stage disease. Investigations of the genetic features of PDAC have demonstrated a frequent occurrence of mutations in genes involved in homologous recombination (HR), especially in the breast cancer susceptibility gene 2 (BRCA2). Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, is approved as a maintenance treatment for patients with advanced PDAC with germline BRCA1/2 mutations following a platinum-containing first-line regimen. Limitations to the use of PARP inhibitors are represented by the relatively small proportion of patients with mutations in BRCA1/2 genes and the modest capability of these substances of inducing objective response. We have previously shown that pancreatic cancer with BRCA2 mutations exhibits a remarkably enhanced sensitivity towards tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) receptor-stimulating agents. We thus aimed to investigate the effect of combined treatment with PARP inhibitors and TRAIL receptor-stimulating agents in pancreatic cancer and its dependency on the BRCA2 gene status. The respective effects of TRAIL-targeting agents and the PARP inhibitor olaparib or of their combination were assessed in pancreatic cancer cell lines and patient-derived organoids. In addition, BRCA2-knockout and -complementation models were investigated. The effects of these agents on apoptosis, DNA damage, cell cycle, and receptor surface expression were assessed by immunofluorescence, Western blot, and flow cytometry. PARP inhibition and TRAIL synergized to cause cell death in pancreatic cancer cell lines and PDAC organoids. This effect proved independent of BRCA2 gene status in three independent models. Olaparib and TRAIL in combination caused a detectable increase in DNA damage and a concentration-dependent cell cycle arrest in the G2/M and S cell cycle phases. Olaparib also significantly increased the proportion of membrane-bound death receptor 5. Our results provide a preclinical rationale for the combination of PARP inhibitors and TRAIL receptor agonists for the treatment of pancreatic cancer and suggest that the use of PARP inhibitors could be extended to patients without BRCA2 mutations if used in combination with TRAIL agonists.

Depth of response of induction therapy and consecutive maintenance treatment in patients with RAS wild-type metastatic colorectal cancer: An analysis of the PanaMa trial (AIO KRK 0212)

BackgroundIn patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin [FU/FA], oxaliplatin [FOLFOX] and panitumumab [Pmab]) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial. MethodsCentral radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (</≥) served as threshold. ResultsOut of 248 patients receiving maintenance therapy, 211 were evaluable for DpR analyses (FU/FA + Pmab, n = 106; FU/FA alone, n = 105). The overall DpR in all patients was 56.5%. DpR of induction therapy (42.5%) accounted for the largest proportion (75.2%) of the overall DpR. While greater DpR to induction therapy was significantly associated with prolonged PFS (HR 0.70, 95% CI 0.52–0.93, p = 0.013) and OS (HR 0.38, 95% CI 0.28–0.51, p < 0.001), there was no significant correlation of DpR and maintenance treatment arm. ConclusionsIn the PanaMa trial, the overall DpR was similar to DpR achieved by other epidermal growth factor receptor-based regimens. DpR to induction therapy accounted for three quarters of the total tumour shrinkage potentially suggesting that FOLFOX plus Pmab can be de-escalated following induction without substantially compromising efficacy. DpR to induction therapy was prognostic but not predictive for efficacy of consecutive maintenance therapy. Clinical trial informationNCT01991873.

Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma

ObjectiveARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. MethodsPatients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes. ResultsRucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit. ConclusionsExceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma.

Efficacy and safety of PARP inhibitors in elderly patients with advanced ovarian cancer: a systematic review and meta-analysis

BackgroundPoly-(ADP-ribose)-polymerase (PARP) inhibitors have shown to be effective as maintenance treatment in patients with advanced ovarian cancer. Although most ovarian cancers develop after age 65, older patients are often under-represented...