Understanding the Role of Comparative Clinical Studies in the Development of Oncology Biosimilars.

Biosimilars have the potential to broaden patient access to biologics and provide cost savings for health care systems. During the development of a biosimilar, data that directly compare the proposed biosimilar with the reference product are required. Such comparative data are generated in a stepwise hierarchical process that begins with extensive laboratory-based structural analyses and functional assays.

PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study.

Background: PF-06439535 is a bevacizumab biosimilar. We aimed to compare the efficacy and safety of PF-06439535 with that of reference bevacizumab (Avastin) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods: In this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries.

Demystifying biosimilars: development, regulation and clinical use.

Biologics are an integral component in the treatment of various diseases. However, limited patient access to these medicines remains a significant global challenge, prompting development of safe and effective biosimilars. A biosimilar is 'highly similar to a reference (originator) product, for which there are no clinically meaningful differences between the two products in terms of safety, purity and potency'.

Bevacizumab biosimilars: scientific justification for extrapolation of indications.

The first biosimilar of bevacizumab was approved by the US FDA; other potential biosimilars of bevacizumab are in late-stage clinical development. Their availability offers opportunity for increased patient access across a number of oncologic indications. The regulatory pathway for biosimilar approval relies on the totality of evidence that includes a comprehensive analytical assessment, and a clinical comparability study in a relevant disease patient population.

Long-term Duration of First-Line Axitinib Treatment in Advanced Renal Cell Carcinoma.

Objective: We conducted a retrospective analysis of two clinical trials in treatment-naïve patients (n = 402) with advanced renal cell carcinoma (RCC) treated with axitinib. Our objective was to compare duration of treatment (DT) and clinical outcome in patients who achieved DT >18 months (longer DT) versus ≤18 months (shorter DT).

Patients And Methods: DT, objective response rate (ORR), tumor shrinkage, and overall survival (OS) were summarized for patients with longer and shorter DT.

Overall survival of first-line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study.

Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and safety in 44 Japanese patients and compared the results with 169 non-Japanese patients.

Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study.

Objectives: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma.

Methods: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period.

Axitinib Versus Sorafenib in First-Line Metastatic Renal Cell Carcinoma: Overall Survival From a Randomized Phase III Trial.

Background: In a randomized phase III trial in treatment-naive patients with metastatic renal cell carcinoma (RCC), axitinib versus sorafenib yielded numerically longer progression-free survival (median, 10.1 vs. 6.

Overall Survival Analysis From a Randomized Phase II Study of Axitinib With or Without Dose Titration in First-Line Metastatic Renal Cell Carcinoma.

Background: In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019).

Population pharmacokinetic-pharmacodynamic modelling of 24-h diastolic ambulatory blood pressure changes mediated by axitinib in patients with metastatic renal cell carcinoma.

Background: Increased blood pressure (BP) is commonly observed in patients treated with vascular endothelial growth factor pathway inhibitors, including axitinib. Ambulatory BP monitoring (ABPM) and pharmacokinetic data were collected in a randomised, double-blind phase II study of axitinib with or without dose titration in previously untreated patients with metastatic renal cell carcinoma.

Objective: Aims of these analyses were to (1) develop a population pharmacokinetic-pharmacodynamic model for describing the relationship between axitinib exposure and changes in diastolic BP (dBP) and (2) simulate changes in dBP with different axitinib dosing regimens.

Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial.

Background: In previous clinical trials of patients with metastatic renal-cell carcinoma, patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib. We therefore undertook a phase 3 trial comparing axitinib with sorafenib in patients with treatment-naive metastatic renal-cell carcinoma.

Methods: In this randomised, open-label, phase 3 trial, patients with treatment-naive, measurable, clear-cell metastatic renal-cell carcinoma from 13 countries were stratified by Eastern Cooperative Oncology Group performance status, and then randomly assigned (2:1) by a centralised registration system to receive axitinib 5 mg twice daily, or sorafenib 400 mg twice daily.

Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial.

Background: Population pharmacokinetic data suggest axitinib plasma exposure correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose titration might optimise exposure and improve outcomes. We prospectively assessed the efficacy and safety of axitinib dose titration in previously untreated patients with metastatic renal-cell carcinoma.

Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer.

Purpose: This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC).

Patients And Methods: Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP).

Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors.

Purpose: To evaluate if diastolic blood pressure (dBP) ≥90 mm Hg during axitinib treatment is a marker of efficacy.

Experimental Design: The relationship between dBP ≥90 mm Hg and efficacy was retrospectively explored across 5 phase II studies of single-agent axitinib for the treatment of 4 different tumor types. All patients had baseline BP ≤140/90 mm Hg and were stratified into 2 groups based on in-clinic BP measurements after initiating therapy: those with dBP <90 mm Hg throughout therapy and those with at least 1 dBP ≥90 mm Hg.

Does federal funding for breastfeeding research target our national health objectives?

Objective: To determine the number and dollar amount of federally funded research projects in the area of infant nutrition/breastfeeding/lactation from 1994 to 1996, and the impact of these funded projects on the achievement of our national goals for increasing the rates of breastfeeding initiation and duration.

Methods: Data were obtained from the Computer Retrieval of Information on Scientific Projects database, available through the National Institutes of Health. Abstracts of funded projects were identified, printed, and subjected to content analysis.