Orphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs. Two components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system. Orphan drugs approved in the U.S., EU and Japan had 37.8 %, 24.6 % and 52.4 % market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8 % (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days’s income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5 % out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban residents. The Chinese government can take more responsibility for improving the availability and affordability of orphan drugs through setting up incentive policies and public platforms for sharing of orphan drug information. Control of the high price of orphan drugs, combined with a joint funding model from both government and private enterprise can efficiently reduce the economic burden of affected patients in China.

Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were initiated on atezo + bev between June 2020 and June 2022. The endpoints of this study were the proportion of individuals who discontinued atezo + bev and received subsequent systemic therapies, time to discontinuation (TTD), and time to next treatment. Overall, 825 individuals were eligible (median age 67 years; 80% male). Over a median follow-up of 15.3 months, most (72%) discontinued atezo + bev, with a median TTD of 3.5 months. A minority (19%) received subsequent therapies, with the most common second-line agents being lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). The median time from index to next treatment post-atezo + bev was 5.4 months. Further research is needed to identify the patients who are most likely to benefit from atezo + bev as well as later-line HCC therapies to optimize overall survival.

Background: Regorafenib (R) and Trifluridine/Tipiracil ± bevacizumab (T) are approved for treating refractory metastatic colorectal cancer (mCRC) but their optimal sequence is unclear. This study describes the characteristics/clinical outcomes of patients with mCRC in U.S. clinical practice treated sequentially with R-T or T-R. Methods: A retrospective cohort study of 818 patients treated with R-T or T-R between January 2015 and November 2022 was conducted using an electronic health record-derived database. The primary objective was to describe the demographic/clinical characteristics and biomarker status of patients treated with R-T or T-R, stratified by treatment line/age. Secondary objectives were to evaluate/estimate the frequency of neutropenia and myelosuppression-related treatments, the number/type of subsequent therapies, time to treatment discontinuation (TTD), and overall survival (OS). Results: Baseline characteristics were similar among patients who received R-T (n = 393) or T-R (n = 425). Lower rates of moderate/severe neutropenia (26%/12% vs. 32%/16%) and granulocyte colony-stimulating factor/erythropoietin use (22% vs. 24%) were observed with R-T versus T-R. The median TTD was 8.7 months and 8.5 months with R-T versus 8.1 months and 7.9 months with T-R as third- and fourth-line treatment, respectively. The median OS was 13.1 months and 11.6 months with R-T versus 11.5 months and 10.3 months with T-R as third- and fourth-line treatment, respectively. Conclusions: This study did not show a statistically significant difference in OS with R-T versus T-R. Although limited by its retrospective nature, the study suggested R-T may be preferable to T-R given the observed reduction in neutropenia/myelosuppression-related treatments.

Background: Several narrative reports document long-term responses to regorafenib treatment in patients with metastatic colorectal cancer (mCRC). However, no large-scale study has assessed long-term responses and there are no established predictors of potential long-term benefit. We carried out an observational study of characteristics of patients treated in real-world clinical practice in the USA using duration of treatment (DoT) as a surrogate for treatment response. Patients and Methods: This retrospective cohort study used a de-identified electronic health record-derived database and included patients aged ≥18 years with mCRC who initiated regorafenib monotherapy between 1 July 2013 and 30 June 2023. Patient cohorts were defined by DoT ≥4 months (LTR4), ≥5 months (LTR5), or ≥6 months (LTR6) and are not mutually exclusive. Results: Of 2444 patients who initiated regorafenib monotherapy during the study, those with long-term response were analyzed: 544 had LTR4 (22%), 367 had LTR5 (15%), and 250 had LTR6 (10%). Most patients with long-term responses had left-sided tumors (65–70%), Eastern Cooperative Oncology Group performance status of 0/1 (67–68%), and liver metastases (55–61%) and had received prior bevacizumab treatment (60–67%). The median age in each group was 66 years, and patients most frequently initiated regorafenib as third-line treatment (31–33%). Median time to regorafenib discontinuation was 6.0–9.3 months among long-term responders. Conclusions: Most patients with long-term responses to regorafenib had favorable performance status at treatment initiation, left-sided tumors, and liver metastases and had received prior bevacizumab treatment. The study highlights that patients in the real-world setting were able to tolerate and maintain long-term responses to regorafenib treatment.

Atezolizumab plus bevacizumab (atezo+bev) is a standard-of-care 1L treatment for unresectable hepatocellular carcinoma (uHCC). Understanding its adoption and use, clinical outcomes, and subsequent therapies are needed. This retrospective cohort study included 550 patients with uHCC in the US who initiated 1L atezo+bev between June 2020 and April 2023. Medical records were abstracted to describe treatment patterns and outcomes. Of 294 patients who discontinued 1L therapy, 176 patients initiated 2L therapy (2L cohort) and 48 patients didn't initiate 2L therapy after ≥8 weeks of follow-up (No 2L cohort). More of the No 2L cohort had Stage IVb tumors, BCLC stage D, ECOG-PS ≥2, ascites, and hepatic encephalopathy at baseline. The 2L cohort were more likely to discontinue atezo+bev due to disease progression (92.1% vs. 56.3%), and less likely due to toxicity/intolerability (4.0% vs. 10.4%) than the No 2L cohort. OS from 1L atezo+bev initiation was significantly longer in the 2L cohort vs. No 2L cohort (median 23.0 vs. 14.3 months; p < 0.001]). 1L Atezo+bev was clinically active with 256 patients remaining on therapy at last follow-up. Patients who progressed after 1L atezo+bev benefited from additional systemic therapies. Future research analyzing the comparative effectiveness of 2L therapies is needed.

Multiple data sources suggest low frequencies of neurotrophic tyrosine receptor kinase (NTRK) gene fusions across common solid tumors, ranging from 0.18% to 0.30%, making it a relevant target for a tumor-agnostic development using a single-arm basket trial. The objective of this study was to explore a multifaceted approach to building a pooled real-world dataset of patients with select solid tumors harboring NTRK1-3 gene fusions from multiple clinicogenomic databases (CGDBs) and clinical site sources. A novel approach was explored for identifying patients with NTRK gene fusion-positive solid tumors from real-world data (RWD) sources through existing CGDBs and global clinical site surveys. CGDBs were assessed for inclusion based on patient data, genomic testing, and accessibility of patient-level data. The clinical site surveys were used to determine the practicality of designing a chart review study where patients were identified via electronic medical records and molecular assays. Approximately 19% of CGDBs and 1% of the clinical sites included in the survey outreach were eligible for inclusion. Combining data from CGDBs and clinical sites through a retrospective chart review yielded a real-world cohort of 512 patients with NTRK gene fusion-positive solid tumors. The rarity of patients with NTRK gene fusion-positive cancer and number of eligible CGDBs/clinical sites present challenges for the identification of sufficient RWD sources that can be used in comparative effectiveness studies to contextualize results from single-arm trials. This approach provides a potential solution to identify fit-for-purpose RWD to support precision medicine for patients with cancer harboring rare genomic alterations.