Articles in medical journals add to the scientific body of research that ultimately influences care. On rare occasions a single study changes the practice of medicine, but in general most clinical research reports contribute to a body of evidence that becomes part of the fabric of clinical decision making, including individual decisions of physicians and patients as well as use in guidelines and recommendations of professional societies and governmental agencies.
In this issue of JAMA, Rugo and colleagues1 report findings from a multicenter clinical trial that may influence care for patients with breast cancer around the world. The authors evaluated the equivalence of a proposed trastuzumab biosimilar compared with the standard therapy, the humanized monoclonal antibody trastuzumab, for achieving overall response and for safety among 458 women without prior treatment for ERBB2 (HER2)–positive metastatic breast cancer.
The overall response rate (ie, complete or partial clinical response) at 24 weeks for the proposed biosimilar plus a taxane was 69.6% (95% CI, 63.62% to 75.51%) compared with 64.0% (95% CI, 57.81% to 70.26%) for trastuzumab plus a taxane. The overall response rate ratio (1.09 [90% CI, 0.97 to 1.21]) and overall response rate difference (5.53 [95% CI, −3.08 to 14.04]) met predefined criteria for equivalence. The rates of adverse events were similar in the 2 treatment groups. The results of this investigation are promising, but as the authors rightfully acknowledge, further research is needed to assess safety as well as long-term clinical outcomes.
Trastuzumab combined with chemotherapy has improved survival for patients with ERBB2-positive metastatic breast cancer. However, because of its high cost (approximately $64 000 for treatment over 1 year),2 trastuzumab is not widely available for patients in some countries. The availability of a biosimilar agent that achieves equivalent clinical outcomes at lower cost could enable many patients with breast cancer to have access to a therapy that may improve survival. Moreover, given the large number of patients with breast cancer, widespread use of this trastuzumab biosimilar evaluated by Rugo et al (if approved for use by the US Food and Drug Administration [FDA], the European Medicines Agency, and other regulatory agencies) also could have financial implications for the manufacturer of this product.
The study by Rugo et al was sponsored by Mylan NV (Canonsburg, Pennsylvania) and Biocon Research Limited (Bangalore, India), codevelopers of the proposed biosimilar trastuzumab and 5 other biologic products. Mylan has recently attracted attention because of the pricing, promotion, and involvement in the health policies of schools regarding one of its products, injectable epinephrine (EpiPen).3 There has been substantial criticism of the company by patients, physicians, and politicians about the recent price increase and the subsequent introduction of a generic epinephrine product by the same company.3
For JAMA, editorial decisions primarily involve evaluation of the scientific validity and merit of research reports, including thorough, rigorous peer review by content experts, in-depth statistical review, and intense editorial scrutiny. However, editorial evaluations and decisions do not occur in a vacuum. For the study by Rugo et al, the editorial evaluation and discussion also included whether concerns about the behavior of one of the study sponsors with respect to pricing of a product should influence the decision to publish a research report sponsored by that company about a different product. In addition, 4 employees of Mylan and 3 employees of Biocon Research are coauthors of the article by Rugo et al, and the sponsors had an important role in study design, data collection and analysis, and drafting of the manuscript for publication. A key consideration was whether publication of this study in JAMA, with its extensive reach in the United States and around world, would reward a company whose behavior with regard to pricing had raised numerous ethical concerns.
Ultimately, the decision to publish this article was based on the determination that the scientific merit and potential to contribute meaningful clinical information for care of patients with breast cancer outweighed other considerations. The controversy over the pricing of drugs in the United States4,5 and around the world is an ongoing debate, and not unique to 1 company or 1 product. The authors have provided assurance to the editors that the study was conducted ethically and appropriately. The lead academic author indicates that she had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The data from this study will also be subject to additional scrutiny by regulatory agencies in making determinations about approval of the proposed trastuzumab biosimilar product.
Whether this study will prove to be truly practice changing remains to be seen. That is a function of whether this biosimilar will become available to patients who are currently unable to access trastuzumab, which will depend to a large degree on financial considerations. Because of the ability to leverage preceding research and development using the standard agents, biosimilars such as the proposed trastuzumab biosimilar evaluated in the study by Rugo et al are expected to save costs in their manufacture. These drugs are a potential solution to the substantially increasing costs of cancer treatment, and introduction of these agents is expected to expand affordability.6
Accordingly, the proposed trastuzumab biosimilar will need to be priced at a level at which patients who otherwise would not have access to expensive therapies such as trastuzumab could receive needed therapy. In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al have expressed their “shared commitment to increasing access to these critical medicines worldwide”7 and indicated that “this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.”7 Ultimately, to fulfill these pledges the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price.
Corresponding Author: Howard Bauchner, MD, JAMA, 330 N Wabash Ave, Chicago, IL 60611 (email@example.com).
Published Online: December 1, 2016. doi:10.1001/jama.2016.18743
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Bauchner H, Fontanarosa PB, Golub RM. Scientific Evidence and Financial Obligations to Ensure Access to Biosimilars for Cancer Treatment. JAMA. Published online December 01, 2016. doi:10.1001/jama.2016.18743