First-line Maintenance Therapy In Patients Research Articles

P227 - Interim results from a real-world ambispective study RAVE-Bladder: avelumab first-line maintenance therapy in patients with metastatic urothelial carcinoma

P227 - Interim results from a real-world ambispective study RAVE-Bladder: avelumab first-line maintenance therapy in patients with metastatic urothelial carcinoma

Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer. In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N=733) were initially treated with a fixed starting dose (FSD) regimen of 300mg every day. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200mg every day in patients with baseline body weight<77kg or baseline platelet count<150,000/µL, and 300mg every day in all other patients. Efficacy and safety outcomes were assessed by starting dose. Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n=317; placebo, n=158) and 258 (35.2%) were assigned to an ISD (niraparib, n=170; placebo, n=88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD. In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen.

Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study

ObjectiveTo evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence. MethodsPost hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population. ResultsIn PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47–0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44–0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46–0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39–0.86) and 0.41 (0.27–0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37). ConclusionsIn this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.

Dual Bronchodilator Therapy as First-Line Treatment in Maintenance-Naïve Patients with Symptomatic COPD: A Pre-Specified Analysis of the EMAX Trial.

IntroductionLimited prospective evidence is available to guide selection of first-line maintenance therapy in patients with COPD. This pre-specified analysis of the EMAX trial explored the efficacy and safety of dual- versus mono-bronchodilator therapy in maintenance-naïve and maintenance-treated patients.MethodsThe 24-week EMAX trial evaluated lung function, symptoms (including rescue medication use), exacerbations, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. Maintenance-naïve and maintenance-treated subgroups were defined by maintenance bronchodilator use 30 days before screening.ResultsThe analysis included 749 (31%) maintenance-naïve and 1676 (69%) maintenance-treated patients. For both subgroups, improvements from baseline in trough FEV1 at Week 24 (primary endpoint) were greater with umeclidinium/vilanterol versus umeclidinium (mean difference [95% CI]; maintenance-naïve: 44 mL [1, 87]; maintenance-treated: 77 mL [50, 104]), and salmeterol (maintenance-naïve: 128 mL [85, 171]; maintenance-treated: 145 mL [118, 172]), and in rescue medication inhalations/day over 24 weeks versus umeclidinium (maintenance-naïve: −0.44 [−0.73, −0.16]; maintenance-treated: −0.28 [−0.45, −0.12]) and salmeterol (maintenance-naïve: −0.37 [−0.66, −0.09]; maintenance-treated: −0.25 [−0.41, −0.08]). In maintenance-naïve patients, umeclidinium/vilanterol numerically improved scores at Week 24 for Transition Dyspnea Index versus umeclidinium (0.37 [−0.21, 0.96]) and versus salmeterol (0.47 [−0.10, 1.05]) and Evaluating Respiratory Symptoms–COPD versus umeclidinium (−0.26 [−1.04, 0.53]) and versus salmeterol (−0.58 [−1.36, 0.20]), with similar improvements seen in maintenance-treated patients. All treatments were well tolerated across both subgroups.ConclusionSimilar to maintenance-treated patients, maintenance-naïve patients receiving umeclidinium/vilanterol showed greater improvements in lung function and symptoms compared with patients receiving umeclidinium or salmeterol. These findings provide support for the consideration of dual bronchodilator treatment in symptomatic maintenance-naïve patients with COPD.

PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta-analysis.

Up to 70% of patients with advanced ovarian cancer have a relapse after primary therapy. New agents and approaches are urgently needed to avoid or slow down this recurrence. To investigate the efficacy of PARP inhibitors (PARPis) as maintenance treatment in patients with newly diagnosed advanced ovarian cancer. PubMed, MEDLINE, EMBASE, Cochrane Library and Web of Science databases. All randomised clinical trials (RCTs) that compared PARPis with placebo as first-line maintenance therapy in ovarian cancer. Two reviewers extracted data. Pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated. PARPis were associated with significant improvement of progression-free survival (PFS) in advanced epithelial ovarian cancer (AeOC) (HR=0.53, 95% CI0.40-0.71; P<0.0001). The benefit was not only in women with BRCA mutations (HR=0.35, 95% CI 0.29-0.42; P<0.00001) and homologous recombination deficiency (HRD) (HR=0.43, 95% CI 0.32-0.60; P<0.00001), but also in those with nonmutated BRCA (HR=0.72, 95% CI 0.63-0.82; P<0.00001) and even non-HRD (HR=0.83, 95% CI 0.70-0.99; P=0.04). PARP inhibitors are effective as maintenance therapy among patients with newly diagnosed advanced ovarian cancer after platinum-based chemotherapy, regardless of BRCA mutation or HRD status. PARPis provide a significant PFS benefit as first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

Ethnic Differences in Persistence with COPD Medications: a Register-Based Study.

Long-acting bronchodilators (LABDs) are recommended as a first-line maintenance therapy in patients with moderate or severe chronic obstructive pulmonary disease (COPD). The aim of the study was to explore potential ethnic differences in persistence with LABD in COPD patients. A cohort of COPD patients diagnosed in 2003-2007 in Copenhagen, Denmark, was followed for 2years in the Danish national registers. According to the number of the LABD medications dispensed, individuals were categorized into three therapy groups: monotherapy, drug combination therapy, and multiple drug therapy. Persistence was defined as the period from the first prescription date to the date of discontinuation. Treatment was considered discontinued if the interval between the two prescriptions was longer than the number of days of cumulative medication supply according to defined daily doses plus 7days. In total, 1129 incident COPD patients using LABDs were included; 6.7% had other than Danish ethnic background. Survival analyses showed that in the cases where LABD medication combination presented COPD maintenance therapy, ethnic background was associated with the higher risk of the therapy discontinuation: HR=1.40, 95% CI=1.03-1.90, p=0.03. There were no ethnic differences in persistence in the monotherapy or multiple therapy groups. COPD patients with other than Danish ethnic background discontinued COPD maintenance therapy more often than ethnic Danes. Attention to the barriers of persistent COPD medication use in COPD patients from ethnic minorities should be payed to facilitate better COPD management.

Efficacy of erlotinib as first-line maintenance therapy in patients with locally advanced or metastatic nonsmall cell lung cancer who have not experienced disease progression or unacceptable toxicity during chemotherapy.

Background:First-line maintenance with erlotinib in nonsmall cell lung cancer (NSCLC) patients without progression after four cycles of chemotherapy was well tolerated and significantly prolonged progression-free survival (PFS) compared with placebo.Aim and Design:This open-label, single arm, Phase IV, interventional study was designed to evaluate erlotinib as first-line maintenance after chemotherapy in Indian NSCLC patients. Primary efficacy objective was to evaluate PFS rate (PFSR) at week 52 and secondary objectives were determination of PFS, overall survival (OS), overall response rate (ORR), disease control rate, and safety.Subjects and Methods:Patients were treated with erlotinib until disease progression/death/unacceptable toxicity or end of study. Patients with disease progression underwent scheduled clinical assessments every 12 weeks thereafter. Kaplan–Meier estimates were used to evaluate PFSR, PFS, and OS. The ORR was summarized using number and percentage along with two-sided 95% Clopper–Pearson confidence interval. The incidence of adverse events (AEs) and serious AEs (SAEs) was tabulated according to severity, outcome, and relationship to erlotinib.Results:Of the 51 enrolled patients, 47 patients completed the study (2: Continuing treatment, 41: Disease progression, and 4: Death) and four patients discontinued treatment (3: Lost to follow-up; 1: Withdrew consent). PFSR was 22.5% at 12 months, median PFS 99 days (14.14 weeks), and median OS was 671 days (22 months). The probability of OS was 74.5% at 14 months. The ORR was 25.5%, and disease control rate was 55.3%. AEs were reported in 62.7% and SAE in 7.8% of patients. Common AEs were diarrhea and rash.Conclusions:Erlotinib was well tolerated by Indian patients in first-line maintenance setting and resulted in median PFS of 14 weeks and median OS of 22 months better than previously reported and with no new safety concerns in this population.

1262P - Erlotinib in routine clinical practice for first-line maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC)

1262P - Erlotinib in routine clinical practice for first-line maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC)