Real-world data on patients with early breast cancer who were prescribed abemaciclib adjuvant therapy in Japan.

Aim: To understand the real-world use of abemaciclib in Japanese patients with early breast cancer (EBC). Methods: This retrospective observational study was conducted using a Japanese administrative claims database in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative EBC who received abemaciclib adjuvant therapy from December 2021-March 2023. Patient characteristics and treatment patterns were summarized. Results: Among 374 patients, 38.2, 51.6 and 63.4% patients received neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy, respectively; 13.1% were chemotherapy naive. Tamoxifen (37.7%), letrozole (35.6%), anastrozole (24.3%) were the commonly prescribed concomitant adjuvant endocrine therapies. Abemaciclib dose reductions were observed in 42.0% patients. Conclusion: Use of abemaciclib for treatment of high-risk EBC was described, which could help inform patient selection and treatment patterns.

Abemaciclib (150 mg twice daily) is prescribed with hormonal therapy for the treatment of early breast cancer (EBC) with high risk of recurrence. We used a big database from Japan that has anonymized information about 44 million patients from 480 hospitals. We aim to describe the characteristics of patients with EBC who receive abemaciclib and their treatment patterns in Japan.We included 374 patients with EBC who had breast cancer surgery and were prescribed abemaciclib with hormonal therapy between December 2021 and March 2023. The median age of patients is 54 years, almost all (99.2%) are female. The most commonly prescribed hormonal therapy with abemaciclib is tamoxifen (37.7%), letrozole (35.6%) and anastrozole (24.3%).Of the 374 patients who were prescribed abemaciclib, 38.2% patients received chemotherapy before surgery, 51.6% received chemotherapy after surgery and 63.4% received radiation therapy after surgery; whereas, 13.1% received no perioperative chemotherapy before abemaciclib therapy. Around 42% of patients reduced their dose from starting dose of abemaciclib. Higher proportion of older patients and patients with low body weight, had dose reduction. Majority of the patients are prescribed either an antidiarrheal agent or probiotic within a day of starting abemaciclib.This is the first study describing patient characteristics and treatment patterns of Japanese patients who are prescribed abemaciclib in the clinical practice. The results will help understand who can benefit from abemaciclib, and to choose the most appropriate patients to receive abemaciclib for the treatment of EBC.

[Efficacy and Safety Analysis of Selpercatinib in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer-Results from the Japanese Subset of a Global Phase 1/2 Study].

PURPOSE: Selpercatinib is a highly selective, potent, rearranged during transfection(RET)inhibitor. A global, multicenter, open-label, phase 1/2 study of selpercatinib(LIBRETTO-001, NCT03157128)has been ongoing since 2017. We evaluated the data of Japanese patients with RET fusion-positive non-small cell lung cancer(NSCLC)using 30 March 2020 cut-off data. METHODS: Phase 2 of LIBRETTO-001 started after confirming the safety of the recommended phase 2 dose(160 mg bid, orally, 28-day cycles)in Japanese. The primary endpoint was the independently assessed objective response rate(RECIST v1.1). RESULTS: Japanese NSCLC patients, including 44 patients in cohort 1 who had previously received platinum-based(or other)chemotherapy, programmed cell death-1/programmed death-ligand 1 immunotherapy, or both, and four previously untreated patients in cohort 2, were analyzed. The objective response rate was 55.3%(95% confidence interval: 38.3, 71.4; one confirmed complete response, 20 confirmed partial responses)in 38 evaluable patients in cohort 1 who could be followed for ≥2 post-baseline scans. The only evaluable patient in cohort 2 had no response. The most frequent treatment- emergent adverse events were increased alanine aminotransferase, increased aspartate aminotransferase, and diarrhea. CONCLUSIONS: Selpercatinib appeared to be effective in Japanese patients with RET fusion-positive NSCLC, and the safety profile was not substantially different from published results.

Safety and effectiveness of ramucirumab and docetaxel: a single-arm, prospective, multicenter, non-interventional, observational, post-marketing safety study of NSCLC in Japan.

BACKGROUND: This study evaluated the safety and effectiveness of ramucirumab and docetaxel for non-small cell lung cancer (NSCLC) in real-world settings. RESEARCH DESIGN AND METHODS: This single-arm, prospective, multicenter, non-interventional, post-marketing study was conducted in Japan between August 2016 and January 2020. Patients diagnosed with unresectable advanced/recurrent NSCLC were eligible for study inclusion. Data on adverse events (AEs) and survival were collected electronically. RESULTS: Of 401 enrolled patients, 398 were eligible for study inclusion. Most patients were male (68.6%) with a median age of 67.0 years. Patients were predominantly diagnosed with adenocarcinoma (78.1%) or squamous cell carcinoma (16.6%); 46.2% received prior treatment with bevacizumab and 38.7% with immune-checkpoint inhibitors. AEs (any grade) were observed in 323 patients (81.2%; grade ≥ 3: n = 174, 43.7%). The most common AEs (any grade) were malaise (14.3%), decreased appetite (13.0%), and neutrophil count decrease (11.6%). At 12 months from treatment commencement, 93.2% of patients had discontinued, mostly due to progressive disease (53.4%) or AEs (28.3%). The 12-month survival rate was 56.7% (95% confidence interval: 51.5-61.8). CONCLUSIONS: Data from real-world settings demonstrate ramucirumab and docetaxel treatment appears to be tolerable and effective in Japanese patients regardless of patient baseline characteristics and prior treatment.

Applicability of Selective Data Collection to Cancer Clinical Studies for Supplemental Marketing Approvals: Frequency of Adverse Reactions Observed During Supplemental Approval Compared With First Approval.

BACKGROUND: In 2012, the US Food and Drug Administration (FDA) issued the draft guidance "Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and Postapproval Clinical Investigations." The selective data collection approach proposed in this guidance leads to reductions in costs and work time and may improve the quality of the database for clinical trials. The current study evaluated the applicability of selective data collection for oncology drugs. METHODS: The labeling information of oncology drugs obtained supplemental approvals from the FDA between 2005 and 2014 were used. The frequency of adverse reactions observed in clinical trials between the first approval and supplemental approvals of a specific drug were compared. Paired studies were categorized into the following 4 groups: A, same tumor type and same usage; B, same tumor type and different usage; C, different tumor type and same usage; D, different tumor type and different usage. RESULTS: A total of 46 study pairs for additional drug indications were investigated. In group A, 6 of the 7 pairs showed a high correlation coefficient ( r = 0.988, 0.953, 0.947, 0.935, 0.853, and 0.846). CONCLUSIONS: Selective data collection should be adopted in cases in which the additional indication of a drug is for the same tumor type and usage as the first or previous indication.

[Role of pharmaceutical company pharmacist in provision of drug information for cancer chemotherapy].

Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have gained recognition as key drugs in the treatment of advanced colorectal cancer. In this article, we describe the results of a survey of medical institutions by pharmacists working at a pharmaceutical company. First, questions from medical institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed that most of these questions concerned safety, with many of these addressing side effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to medical institutions. The results indicated that staff are interested in the safety and critical path of these regimens. These results suggest that a lot of medical institutions require more information from pharmaceutical companies. This indicates that pharmacists should do more to take the needs of medical institutions into account in providing improved customer support.

[What happened during these 12 years since CPT-11 was launched in Japan ?].

CPT-11 (irinotecan hydrochloride, trade name: Campto or Topotecin) was launched in 1994. L-OHP (oxaliplatin, trade name: Elplat) was approved based on the fast track evaluation system and launched in 2005. Originally, both of these drugs were synthesized in Japan. Just after the launch of CPT-11, the severity of its toxicity was reported more frequently than its efficacy, therefore it spent much time to spread the use of this drug. As for L-OHP, the approved regimen is FOLFOX in spite the regimen was not actually studied in its registration studies in Japan. However, L-OHP is widely used after its launch. Thus, we find a progress in terms of regulatory system to introduce the widely accepted standard chemotherapy to the Japanese practice sites rapidly. We also find a further understanding for cancer chemotherapy in Japanese society. Recently, mass media reported cancer patients who were eager to receive the standard chemotherapy and requesting the regulatory authorities its quick approval. We have never seen such a scene 10 years ago. These patients' activities could be a key factor to change the infrastructure of cancer therapy.