Phase 3 Trial of Selpercatinib in Advanced -Mutant Medullary Thyroid Cancer.

Background: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced -mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear.

Methods: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment.

Selpercatinib in Patients With Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial.

Purpose: Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with fusion-positive non-small-cell lung cancer (NSCLC). We provide a registrational data set update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety.

Methods: Patients were enrolled to LIBRETTO-001, a phase I/II, single-arm, open-label study of selpercatinib in patients with -altered cancers.

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial.

Background: Selpercatinib is a first-in-class, highly selective RET kinase inhibitor with CNS activity that has shown efficacy in RET fusion-positive lung and thyroid cancers. RET fusions occur rarely in other tumour types. We aimed to investigate the efficacy and safety of selpercatinib in a diverse group of patients with RET fusion-positive non-lung or thyroid advanced solid tumours (ie, a tumour-agnostic population).

Quality of life of patients with soft tissue sarcoma treated with doxorubicin in the ANNOUNCE phase III clinical trial.

Background: Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy.

Methods: ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo.

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001.

Introduction: Immune checkpoint inhibitor (ICI) therapy has been found to increase the risk/severity of immune-mediated adverse events with subsequent kinase inhibitor treatment in oncogenically driven cancers. We explored the risk for hypersensitivity with selpercatinib, a first-in-class highly selective and potent, central nervous system-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive NSCLC compared with their ICI-naive counterparts.

Methods: Data from patients enrolled by December 16, 2019, in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms of hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by greater than or equal to 1 of the following signs/symptoms: thrombocytopenia, increased aspartate aminotransferase or alanine aminotransferase, hypotension, tachycardia, or increased creatinine.

Phase III study of selpercatinib versus chemotherapy ± pembrolizumab in untreated positive non-small-cell lung cancer.

Selpercatinib, a novel, highly selective and potent, inhibitor of , demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pretreated and treatment-naive fusion-positive non-small-cell lung cancer patients in a Phase I/II clinical trial. LIBRETTO-431 (NCT04194944) is a randomized, global, multicenter, open-label, Phase III trial, evaluating selpercatinib versus carboplatin or cisplatin and pemetrexed chemotherapy with or without pembrolizumab in treatment-naive patients with locally advanced/metastatic fusion-positive nonsquamous non-small-cell lung cancer. The primary end point is progression-free survival by independent review.

Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial.

Importance: Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone.

Objective: To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS.

A phase 1b study of necitumumab in combination with abemaciclib in patients with stage IV non-small cell lung cancer.

Objectives: Necitumumab, an anti-EGFR antibody, and abemaciclib, a CDK4/6 inhibitor, have shown activity in patients with non-small cell lung cancer (NSCLC) and have non-overlapping toxicities. A 2-part, single-arm, multicenter, phase 1b trial was conducted to test the safety and efficacy of necitumumab plus abemaciclib in patients with advanced NSCLC who had received ≤2 lines of chemotherapy, including a platinum-based one.

Materials And Methods: Part A was a dose-escalation phase for abemaciclib (100, 150, 200 mg, Q12 H) in combination with necitumumab 800 mg D1D8 Q3W to determine the recommended dose for the expansion cohort, Part B.

First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

Background: The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting.

Methods: The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy.

Venous thromboembolism with EGFR monoclonal antibody necitumumab in stage IV non-small cell lung cancer: A retrospective cohort analysis.

Introduction: Metastatic non-small cell lung cancer (NSCLC) is a recognized risk factor for VTE. Some systemic treatments may increase this risk further. Here, we present the risk of VTE and its prognostic significance for patients treated with chemotherapy (chemo) and the EGFR monoclonal antibody necitumumab (neci) for metastatic NSCLC.

Efficacy and Safety of First-Line Necitumumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in East Asian Patients with Stage IV Squamous Non-small Cell Lung Cancer: A Subgroup Analysis of the Phase 3, Open-Label, Randomized SQUIRE Study.

Purpose: The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1,093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study.

Materials And Methods: All patients received up to six 3-week cycles of gemcitabine (days 1 and 8, 1,250 mg/m²) and cisplatin (day 1, 75 mg/m²).

Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE).

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors.

Patient And Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone.

The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial.

Introduction: Necitumumab, a second-generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine-cisplatin compared with those who received gemcitabine-cisplatin. Here we characterize health-related quality of life (HRQoL) and tolerability results.

Methods: A total of 1093 patients with stage IV squamous non-small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine-cisplatin (gemcitabine = 1250 mg/m(2) IV on days 1 and 8; cisplatin = 75 mg/m(2) IV on day 1) or gemcitabine-cisplatin alone (every 21 days) for up to six cycles.

A randomized Phase 2 study of pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in patients with completely resected stage IB or II Non-Small-Cell Lung Cancer.

Objectives: We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC).

Materials And Methods: Patients in this multicenter, open-label, parallel-group, non-comparative Phase 2 study were randomized (1:1) to pemetrexed (500 mg/m(2)) with either cisplatin (75 mg/m(2)) or carboplatin (AUC5) for 4 cycles of 21 days. The primary endpoint was treatment feasibility (defined as 4 cycles completed with no cycle delay >42 days and ≤2 dose reductions, with a median relative dose intensity (RDI) ≥95% [overall]; and no Grade ≥3 toxicities at the follow-up visit 30 days after last drug administration).

Final results from a Phase II study of pemetrexed and cisplatin with concurrent thoracic radiation after Pem-Cis induction in patients with unresectable locally advanced non-squamous non-small cell lung cancer (NSCLC).

Objectives: This single-arm multicenter Phase II study investigated the efficacy and safety of pemetrexed (Pem) and cisplatin (Cis) induction chemotherapy (CT) followed by full-dose Pem-Cis plus concurrent radiotherapy (RT) in patients with locally advanced non-squamous NSCLC.

Materials And Methods: Patients with unresectable Stage III non-squamous NSCLC received two 21-day cycles of Pem 500 mg/m(2) (vitamin/folic acid supplementation and dexamethasone prophylaxis per Pem-label)+Cis 75 mg/m(2) on Day 1. Eligible patients who had not progressed continued with 2 further cycles of full-dose Pem-Cis plus concurrent RT (2 Gy/fraction, 5 days/week, 66 Gy total).

Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study.

Background: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated, stage IV, non-squamous non-small-cell lung cancer (NSCLC).

Methods: We did this randomised, open-label, controlled phase 3 study at 103 sites in 20 countries.

A phase II single-arm study of induction chemotherapy with cisplatin and gemcitabine followed by concurrent cisplatin and gemcitabine with thoracic radiation for unresectable locally advanced non-small cell lung cancer.

Objectives: The aim of this study was to evaluate the efficacy and tolerability of the combination of cisplatin-gemcitabine with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).

Methods: This was a phase II, multicenter, open-label, single-arm trial in treatment-naïve patients with stage IIIA and IIIB LA-NSCLC. After three induction cycles with gemcitabine 1250 mg/m(2) plus cisplatin 80 mg/m(2), two concurrent chemoradiotherapy cycles with gemcitabine 300 mg/m(2), cisplatin 80 mg/m(2), and radiotherapy (63 Gy) were administered.

A randomized phase II non-comparative study of pemetrexed‑carboplatin and gemcitabine‑vinorelbine in anthracycline- and taxane-pretreated advanced breast cancer patients.

Pemetrexed-carboplatin and gemcitabine‑vinorelbine combination therapies were efficacious in phase II and phase III studies as first-line breast cancer treatment. Thus, Arm A and Arm B combinations were investigated in patients pretreated with anthracycline and taxanes. Women with advanced breast cancer, with ≥1 measurable lesion per RECIST, were stratified by line of treatment (1st, 2nd), visceral disease (yes/no), ECOG PS (0-1 vs.

Second-line therapy for non-small cell lung cancer in clinical practice: final results and treatment pathways from the SELECTTION observational study.

Objectives: SELECTTION was a multinational, prospective observational study to assess the choice of and the time from initiation of second-line treatment to treatment discontinuation for any reason in patients with non-small cell lung cancer.

Methods: Treatment cohorts were constructed based on prescribed second-line treatments that were at the discretion of the treating physicians, for 1013 patients enrolled in 11 countries. Propensity score analysis was conducted to assess whether the cohorts were comparable.

Second-line treatment of stage III/IV non-small-cell lung cancer (NSCLC) with pemetrexed in routine clinical practice: evaluation of performance status and health-related quality of life.

Background: Second-line treatment of advanced non-small-cell lung cancer (NSCLC) improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS) and health-related quality of life (HR-QoL) during second-line pemetrexed treatment in routine clinical practice.

Taxane-based mono- or combination therapy for managing metastatic breast cancer (MBC) in routine practice: a multinational prospective observational study.

Objectives: Taxanes are standard for first-line chemotherapy of metastatic breast cancer (MBC), but indications for single-agent versus combination treatment remain controversial. This non-interventional study in 12 different countries explored treatment patterns and progression-free survival (PFS) in routine practice.

Research Design And Methods: The prospective study was designed to determine factors associated with the choice of taxane-based regimens for MBC.

Second-line therapy for NSCLC in clinical practice: baseline results of the European SELECTTION observational study.

Objective: Although the efficacy of a number of drugs for the second-line treatment of non-small cell lung cancer (NSCLC) has been demonstrated in Phase III trials, very limited evidence exists on optimal duration of second-line treatment or the reasons why this treatment is stopped in standard clinical practice. SELECTTION (Survey in European Lung Cancer Evaluating Choice of Treatment and Tolerability In Observed NSCLC) was designed to assess the time from initiation of second-line treatment for NSCLC to treatment discontinuation for any reason, the reasons for discontinuation, and the impact of discontinuation on outcomes.

Methods: From October 2006 to January 2008, 1012 patients with advanced/metastatic NSCLC who completed or discontinued first-line treatment were enrolled in a multi-national, prospective observational cohort study (SELECTTION).

Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: a 6-week, randomized, placebo-controlled, double-blind trial in Russia.

The objective of the study was to compare the efficacy and tolerability of once-daily atomoxetine (< or =1.8 mg/(kg day) with those of placebo in children and adolescents (aged 6-16 years) with attention-deficit/hyperactivity disorder [ADHD (DSM-IV)]. This randomized, placebo-controlled, double-blind trial was conducted in Russia.