The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) created an abbreviated licensure pathway in the United States that allows for the development and approval of biologic products shown to be biosimilar to or interchangeable with a US Food and Drug Administration (FDA)-licensed reference product. FDA released the draft guidance for industry on Demonstrating Interchangeability with a Reference Product (hereafter referred to as the Draft Interchangeability Guidance) in January 2017. Despite FDA's efforts, there continues to be a great deal of confusion and misinformation surrounding the topic of interchangeability. Here we discuss interchangeability, as well as substitution of biological products, with a focus on the US. Additionally, the separate topic of physician-mediated switching is covered and distinguished from interchangeability and substitution.

Aim: To describe treatment patterns and patient and provider characteristics associated with the recently introduced biosimilar rituximab-pvvr. Methods: This retrospective analysis included adult patients with one or more claims for rituximab-pvvr, with an index date of 23 January 2020 and a study period covering 1 January 2019–31 July 2020. Results: Of 249 patients included, the most common rituximab-pvvr indications were non-Hodgkin’s lymphoma (77.5%) and chronic lymphocytic leukemia (11.2%). Some patients with non-Hodgkin’s lymphoma (42.5%) and chronic lymphocytic leukemia (39.3%) switched to rituximab-pvvr from the reference product or another rituximab biosimilar. Most patients were aged ≥65 years (63.5%) and were male (54.6%). Most (59.0%) rituximab-pvvr prescribers practiced in the south of the USA. Conclusion: Utilization occurred in approved and extrapolated indications. These preliminary findings suggest switching between reference product and rituximab biosimilars; rituximab-pvvr combination regimens are being adopted in real-world oncology practice.

108 Background: In the US, rural areas have higher cancer mortality rates than urban areas. Clinical practice guidelines recommend testing for BRAF and RAS mutations, and deficient mismatch repair (dMMR)/microsatellite instability (MSI) in pts with mCRC. However, data on biomarker testing rates in rural communities are limited. We surveyed ONC in the US who practice in rural areas and urban clusters to identify biomarker testing patterns and barriers. Methods: A web-based survey was administered to board-certified ONC who spend ≥ 40% of their time providing direct care to pts in rural areas or urban clusters (US Census Bureau definition) and who treated ≥ 2 pts with stage IV mCRC in the month prior to the survey. ONC in Maine, Vermont, and West Virginia were excluded (state legislature), as were those employed by the US government, Veterans Affairs, or Kaiser Permanente. Respondents were compensated. Data were analyzed descriptively. Results: From Feb 12 to Mar 18, 2021, 99 ONC (40% medical ONC, 60% hematologists/ONC) completed the survey. Respondents spent 56% and 18% of their time (mean) practicing in urban clusters and rural areas, respectively; 33% were in the South, followed by 26%, 22%, and 18% in the Northeast, Midwest, and West, respectively. 97% of ONC had ordered biomarker tests for pts; 35% referred pts for independent genomic testing. ONC tested biomarkers most commonly for stage IV disease: 72%, 65%, 63%, 59%, and 66% for KRAS, NRAS, BRAF, PD-L1, and dMMR/MSI, respectively (Table). 41% of ONC reported performing reflex testing at their primary practice, most commonly for PD-L1 (62%), KRAS (60%), and dMMR/MSI (52%). DNA-based next-generation sequencing (NGS) was the most common testing method reported. ONC indicated they would test for an actionable biomarker if it were known to occur in ≥ 28% of pts with mCRC. The most commonly cited barriers to testing were insufficient tissue samples and lack of insurance coverage. Although > 50% of ONC agreed telehealth can improve testing rates, 81% noted barriers, including pts lacking technology equipment (56%) and pts being disengaged or unwilling to use telehealth (37%). Further data on testing-related decision making and barriers will be presented. Conclusions: Biomarker testing in rural areas and urban clusters falls short of current guideline recommendations. Further exploration of rural biomarker testing practices and strategies to improve testing are needed.[Table: see text]

Background Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody. Objective Our objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera ® ) in patients with CD20+ low-tumor-burden follicular lymphoma. Patients and methods Rituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m 2 ) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks. The relationships between infusion rate, drug exposure, and IRR incidence were assessed by logistic regression analysis and pharmacokinetic modeling and simulation. Baseline CD20 level, antidrug antibody (ADA) status, and tumor burden according to IRR occurrence (yes/no) were compared descriptively. Results Median rituximab infusion duration on day 1 was 3.50 h for each of the two groups. There was a positive correlation between infusion rate and all-grade IRRs occurring within 24 h after infusion (p < 0.0001). Patients who developed IRRs had a higher median baseline CD20+ level. IRR incidence was unaffected by baseline ADA status. Drug exposure did not predict IRR incidence. Baseline tumor burden was similar between patients with and without IRRs. Conclusions Results of this analysis provide a better understanding of IRRs after the first rituximab (RTX-PF or RTX-EU) infusion and demonstrate a potential correlation of infusion rate and other factors with IRR at the individual and population levels. Infusion-rate escalation steps continue to be needed to manage IRRs.

e18778 Background: BRAF mutations are estimated to occur in up to 10% of people with colorectal cancer, 45% with melanoma, and 2-4% with NSCLC and generally represent a poor prognosis for these patients. The National Comprehensive Cancer Network (NCCN) recommends BRAF testing for patients with mCRC, melanoma and NSCLC, however adherence to guidelines and real-world testing rates are not well known. This study describes real-world BRAF testing rates among mCRC, m-melanoma and NSCLC patients. Methods: We performed a retrospective study of adult patients diagnosed with mCRC or m-melanoma from 1/2013 to 11/2020 in the nationwide Flatiron Health EHR-derived de-identified database and with NSCLC from 1/2013 to 11/2020 in the ConcertAI Definitive Oncology Dataset. We measured the proportion of patients receiving a BRAF test and timing of testing in relation to diagnosis and treatment line, concentrating the latter on a limited time frame when there was a stable period of testing (2018-2019 for mCRC and m-melanoma; 2018 for NSCLC). Results: We included 21,758 patients with mCRC, 4,276 patients with m-melanoma, and 12,236 patients with NSCLC of whom 52.7%, 92.0% and 17.2%, respectively, received a BRAF test. Testing rates for mCRC and NSCLC increased over time (mCRC: 27.3% in 2013, 49.9% in 2016, 71.4% in 2020; NSCLC: 6.4% in 2013, 13.5% in 2016 and 29.5% in 2018) and were relatively stable for m-melanoma (94.5% in 2013, 90.6% in 2016, 89.5% in 2020). Among BRAF-tested mCRC patients in 2018-2019 (70.3%, n=5,874), 7.8% were tested before metastatic (m-) diagnosis, with median time from test to m-diagnosis of 8.5 months; 32.1% on or after m-diagnosis and before 1L and 55.8% on or after 1L, with median time from m-diagnosis to test of 1.4 months. Among BRAF-tested m-melanoma patients in 2018-2019 (91.7%, n=1,174), 31.0% were tested before m-diagnosis, with median time from test to m-diagnosis of 9.5 months; 62.2% on or after m-diagnosis and before 1L and 2.5% on or after 1L, with median time from m-diagnosis to test of 0.0 months. Among BRAF-tested NSCLC patients in 2018 (29.5%, n=2,010), 3.0% were tested before earliest diagnosis, with median time from test to diagnosis of 0.3 months; 24.6% on or after earliest diagnosis and before 1L and 15.4% on or after 1L, with median time from diagnosis to test of 1.1 months. (For about 60% of the BRAF-tested patients, it was not possible to identify at which stage of treatment the test was conducted). Conclusions: BRAF testing rates were highest among m-melanoma patients, followed by mCRC and NSCLC. Testing rates for mCRC and NSCLC increased from 2013 to 2020, which may have been in response to guideline changes and availability of targeted treatments. The majority of BRAF testing occurred before 1L in melanoma and NSCLC, and on or after 1L in mCRC.