Melissa Armitage

Regulatory and clinical considerations for biosimilar oncology drugs

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

Adjuvant colon cancer care quality, risk, value, and level one data and guideline compliance among the elderly privately insured in southeastern USA.

249 Background: Oxaliplatin-containing regimens are among the most efficacious adjuvant treatments for locally-advanced colon cancer, although significant toxicity can occur. Because of relevant level I data, the NCCN revised its guidelines in 2012, recommending omission of oxaliplatin from combination adjuvant chemotherapy regimens for older patients (>70yo) with colon cancer. We examined prescribing behavior of oncologists between 2009 and 2014 to evaluate how rapidly NCCN guidelines were adopted into practice. METHODS This is a retrospective observational study of chemotherapy request data from more than 2,000 community oncologists in the southeastern United States. We examined 57 consecutive months of chemotherapy requests for stage II and III colon cancer patients 70 years and older, based on three epochs. During the middle epoch, one phase III trial evaluating oxaliplatin-containing regimens as adjuvant chemotherapy (NSABP C-07), and a revised 2012 NCCN guidelines, each supported omission of oxaliplatin from adjuvant chemotherapy regimens for older persons with colon cancer. Multivariate analyses evaluated associations among patient characteristics (age, gender, and performance status), disease stage, and time-period, with the odds of receiving oxaliplatin-containing regimens as adjuvant chemotherapy. RESULTS Among 266 persons with stage II or III colon cancer 70 years of age and older, over the six-year span, most adjuvant chemotherapy requests (184/266, 69.2%) contained oxaliplatin. Older age, male gender, and poor performance status were associated with significantly lower odds of receiving oxaliplatin-containing adjuvant chemotherapy regimens (p<0.05), while time period (epoch) was not significantly associated with temporal changes in patterns of use. CONCLUSIONS Use of oxaliplatin containing adjuvant chemotherapy regimens among older persons with colon cancer did not decrease following publication of phase III clinical trial data and revised NCCN guidelines recommending against oxaliplatin use in this setting. Focused quality improvement initiatives for this population of cancer patients may be helpful.

Quality and value implications of NCCN-compliant use of maintenance rituximab for patients with low-grade NHL.

36 Background: Rituximab maintenance for indolent, incurable non-Hodgkin lymphoma (NHL) remains controversial. NCCN supports maintenance rituximab for a span of up to two years as an alternative to watchful waiting following induction therapy. At least a dozen scientific papers have been published describing rituximab maintenance results; none has demonstrated overall survival benefit. The strongest data support comes from the PRIMA phase III trial which showed an increased PFS but no survival advantage. Increased toxicity, however, is clear and can be serious. Reports of progressive multifocal leukoencephalopathy, a rapidly fatal neurodegenerative disease, should be of especial concern to patients whose disease course can span many years. Oncology Analytics (OA) enhances cancer care quality and value by providing oncology decision-support to providers in SE USA. We hypothesized that the use of maintenance rituximab in this area of the country produces profound cost and real risk for a highly uncertain benefit to this population. METHODS We reviewed all requests for rituximab maintenance for low-grade NHL submitted by oncology practices to a major health insurer in one US region from Jul 2009-May 2014. We calculated the cumulative cost for blanket approval of such requests and the savings associated with our decision-support discussions of this questionable but NCCN-compliant practice. RESULTS 470 requests for maintenance rituximab for low-grade NHL were initiated within this 59-month span. The proportion of maintenance rituximab requests relative to the total chemotherapy requests decreased consistently over time, from 4.5% in the first six months of OA involvement in 2009, down to 1.5% in May 2014. The annual cost of rituximab maintenance, which depends on the dose schedule, ranges from about

Use, misuse, and overuse of white cell growth factors (GF) in community oncology practices in southeastern United States.

30,000 to

Effect of Oncology Analytics (OA) cancer care quality initiative on inappropriate use of erythropoiesis stimulating agents (ESA) among cancer patients receiving chemotherapy with curative intent.

40,000 per year. Additionally, we discovered many rituximab maintenance requests for durations exceeding two years without evidence-based support, most of which were rescinded after OA intervention. CONCLUSIONS Ongoing OA intervention reduces risk of toxicity and enhances the quality and value of cancer care for these patients.