Chun-Nan Kuo

Purpose: This study aims to compare the effectiveness and safety of standard and reduced initial doses of regorafenib in patients with metastatic colorectal cancer (mCRC). Materials and Methods: This retrospective observational study was conducted using the Taipei Medical University Clinical Research Database. Patients aged 20 years or older who received regorafenib for mCRC between January 2014 and December 2021 were included. Patients were divided into standard initial dose (160 mg) and reduced initial dose (< 160 mg) groups. Time‐to‐treatment discontinuation (TTD), overall survival (OS), and the incidence of five common adverse events were compared between groups. Results: Among 266 patients, 58 received the standard initial dose and 208 received the reduced initial dose; the median TTD was 68.0 days and 64.5 days, respectively ( p = 0.25). The median OS was 9.7 months for the standard‐dose group and 6.7 months for the reduced‐dose group ( p = 0.01). In the multivariate Cox analysis, the reduced initial dose was associated with shorter survival (hazard ratio 1.66 [95% confidence interval 1.22–2.30]). Hand‐foot skin reaction and total bilirubin elevation were less common in the reduced‐dose group ( p = 0.01 and 0.03, respectively). Excluding concurrent anti‐cancer drug users led to a similar median OS between the two dosing groups ( p = 0.12). Conclusion: No difference in TTD was observed between the dosing groups. The reduced‐dose group had a shorter OS but fewer adverse events. For patients who can tolerate standard doses of regorafenib, a combination of regorafenib and other anti‐cancer drugs may be beneficial but would require further investigation.

Purpose: This study aimed to evaluate the prognostic effect of the cumulative dose (CD) of regorafenib on survival in patients with metastatic colorectal cancer (mCRC).Materials and Methods: This retrospective study utilized the Taipei Medical University Clinical Research Database for analysis. Patients aged ≥ 20 years with mCRC who were prescribed regorafenib between January 2014 and December 2021 were identified and then divided into low‐ and high‐CD groups (≤ 4200 mg vs. > 4200 mg). Overall survival (OS), time‐to‐treatment discontinuation (TTD), and the incidence of five common adverse events were compared between groups. In addition, natural cubic splines were employed to examine the non‐linear relationship between cumulative doses and survival in the multivariate Cox regression model.Results: A total of 259 patients were enrolled, with 130 in the low‐CD group and 129 in the high‐CD group; the median OS was 4.6 months and 9.8 months, respectively (p < 0.01). The median TTD was 51.5 days for the low‐CD group and 72.0 days for the high‐CD group (p < 0.01). No significant difference in drug‐related adverse events was observed between groups. In the multivariate Cox analysis, a CD ≤ 4200 mg was a negative prognostic factor (hazard ratio 1.41 [95% confidence interval 1.08–1.84], p = 0.01). In addition, patients on a dose range between 4368 and 5376 mg exhibited minimal mortality risk.Conclusion: The cumulative doses of regorafenib > 4200 mg were associated with improved survival. The suggested optimal dose range serves as a reference for dose modification in clinical practice.

This study was aimed to evaluate the cost-effectiveness of pembrolizumab with chemotherapy (pembrolizumabcombination therapy) and compare it with standard-of-care platinum-based chemotherapy (chemotherapy alone) as a first-line treatment for metastatic nonsquamous NSCLC from the perspective of Taiwan's third-party-payer public health-care system. We used a partitioned survival model with an estimated time horizon of 10 years. The partitionedsurvival model uses KaplaneMeier estimates of progression-free and overall survival from the KEYNOTE-189 clinicaltrial. The quality-adjusted life-year (QALY) values were based on utility values by progression status calculated from theKEYNOTE-189 trial. This study examined costs related to treatment regimens, disease management, second-line therapy,end-of-life care, and adverse event management. Cost and utility were discounted at 3% per year. Probabilistic anddeterministic sensitivity analyses were performed to test the robustness of the results. The willingness-to-pay threshold was set at 3 × Taiwan's gross domestic product (GDP), equivalent to NT$2,788,290. In the base-case scenario, pem-brolizumab combination therapy resulted in an expected gain of 0.89 QALYs and an incremental cost of NT$2,201,203relative to chemotherapy alone. The ICER was NT$2,478,601/QALY. In the analysis of the PD-L1 tumor proportion score (TPS) ≥ 50% subgroup, the patients who received pembrolizumab combination therapy gained 1.12 QALYs more than those who received chemotherapy alone, and the incremental cost was NT$2,522,528. Therefore, the ICER for this subset of patients was NT$2,258,358/QALY. In conclusion, pembrolizumab combination therapy is a cost-effective option forfirst-line treatment of metastatic nonsquamous NSCLC. The relative cost-effectiveness of pembrolizumab combination therapy is greatest for patients with PD-L1 TPS ≥50%.

Patients with cancer taking oral antineoplastic medications may encounter problems including suboptimal adherence as well as physical and psychological disease burden. Despite increase in the use of oncology pharmacy services, there are wide variations between healthcare professionals and patient perceptions of patients' medication experiences. The objective of the study was to explore the medication experience of taking oral targeted therapy in patients with advanced non-small cell lung cancer (NSCLC). We purposively sampled advanced stage (stage III or IV) NSCLC patients taking epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in a medical center in Taiwan. Face-to-face interviews using semi-structured interview guides were conducted. Interviews were transcribed verbatim and thematic analysis was applied. A phenomenological methodology was adopted to explore the underlying meaning of patients' lived experience. A total of 19 participants with a mean age of 68.2 years were interviewed. The duration of EGFR-TKIs use ranged from 2 weeks to 5 years. When first learned about the unexpected yet 'treatable' cancer, participants expressed strong emotional responses based on their intrinsic beliefs of the terminal disease and therapy. They walked along an unfamiliar trail while confronting physical and psychological challenges and made compromises to treatment. Gaining experiences from cancer journey, patients with cancer continuously seek the ultimate goals-'return to normal'. This study also revealed medication experiences of participants' journey from seeking information in the initial phase and living with cancer, to taking back control of their own lives. Healthcare professionals could better empathize with patients' loss of control and understand their perspectives when making clinical decisions. These findings can guide interdisciplinary teams to integrate patients' beliefs and conduct pre-screening assessments of health literacy levels to tailor communication. Subsequent interventions should be developed to identify barriers to medication self-management and empower patients by building social networks.

According to the National Comprehensive Cancer Network and the American Society of Clinical Oncology, the standard treatment for pancreatic cancer (PC) is gemcitabine and fluorouracil. Other chemotherapeutic agents have been widely combined. However, drug resistance remains a huge challenge, leading to the ineffectiveness of cancer therapy. Therefore, we are trying to discover new treatments for PC by utilizing genomic information to identify PC-associated genes as well as drug target genes for drug repurposing. Genomic information from a public database, the cBio Cancer Genomics Portal, was employed to retrieve the somatic mutation genes of PC. Five functional annotations were applied to prioritize the PC risk genes: Kyoto Encyclopedia of Genes and Genomes; biological process; knockout mouse; Gene List Automatically Derived For You; and Gene Expression Omnibus Dataset. DrugBank database was utilized to extract PC drug targets. To narrow down the most promising drugs for PC, CMap Touchstone analysis was applied. Finally, ClinicalTrials.gov and a literature review were used to screen the potential drugs under clinical and preclinical investigation. Here, we extracted 895 PC-associated genes according to the cBioPortal database and prioritized them by using five functional annotations; 318 genes were assigned as biological PC risk genes. Further, 216 genes were druggable according to the DrugBank database. CMap Touchstone analysis indicated 13 candidate drugs for PC. Among those 13 drugs, 8 drugs are in the clinical trials, 2 drugs were supported by the preclinical studies, and 3 drugs are with no evidence status for PC. Importantly, we found that midostaurin (targeted PRKA) and fulvestrant (targeted ESR1) are promising candidate drugs for PC treatment based on the genomic-driven drug repurposing pipelines. In short, integrated analysis using a genomic information database demonstrated the viability for drug repurposing. We proposed two drugs (midostaurin and fulvestrant) as promising drugs for PC.

Background: Primary and recurrent venous thromboembolism (VTE) commonly occur in patients with cancer. However, because of the National Health Insurance regulations, available dosage forms, and clinical conditions, the prescribed dose of rivaroxaban may not be consistent with its recommended dose. Objective: To evaluate the 6-month recurrence rate of VTE and safety of rivaroxaban for patients with cancer. Methods: Patients with new cancer diagnosis or recurrence from 2014 to 2018 who initiated rivaroxaban for VTE from January 2015 to January 2019 were included. We set the rivaroxaban initiation date as the index date and followed up the patients for 180 days. We collected information regarding the starting and maintenance dose/frequency and the treatment duration. The efficacy outcome was the recurrence of VTE within 180 days. The safety outcome included the major bleeding rate and clinically relevant nonmajor bleeding (CRNMB) rate. Results: Approximately, 46.2% of the 65 included patients received a standard starting dose, and 45% of patients received a maintenance dose above 15 mg (median: 23.9 and 13.1 mg per day, respectively). Two-thirds of the patients stopped treatment within 180 days. Recurrent VTE occurred in 2 (3.1%) patients within 6 months. The major bleeding rate was 7.7%, and the CRNMB rate was 3.1%. Conclusion and Relevance: The 6-month recurrence rate of VTE and safety profile were similar between the lower and standard dose of rivaroxaban. This result may be applied to the institutions with dosage availability limited by formulary regulation and patients who cannot use full dose because of clinical considerations.

Objective: To evaluate the effectiveness of the collaboration between oncology pharmacists and anaesthesiologists for improving pain control management in cancer patients. Methods: This retrospective case–control pilot study enrolled inpatients with active cancer and a pain score of >3 at least once per day for 3 consecutive days. The study group was selected from June 2018 to January 2019. Patients with the same inclusion criteria were selected between November 2017 and May 2018 to serve as the comparison group. The primary outcome was the percentage of patients that experienced pain relief within 7 days from initial pain attack. Results: A total of 71 and 77 patients were enrolled in the study and comparison groups. More patients in the study group experienced pain relief within 7 days from the index date (78.9% [56 of 71 patients] versus 72.7% [56 of 77 patients], respectively). The service increased the rate of intervention from attending physicians within 4 days from index date and quality of opioid management. Conclusion: The collaboration between oncology pharmacists and anaesthesiologists for cancer pain management may be associated with an increase in the rate of pain relief in cancer patients with poor pain control.