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  1. Lim GC, Aina EN, Cheah SK, Ismail F, Ho GF, Tho LM, et al.
    BMC Cancer, 2014;14:212.
    PMID: 24650245 DOI: 10.1186/1471-2407-14-212
    BACKGROUND: Cancer is the leading cause of deaths in the world. A widening disparity in cancer burden has emerged between high income and low-middle income countries. Closing this cancer divide is an ethical imperative but there is a dearth of data on cancer services from developing countries.
    METHODS: This was a multi-center, retrospective observational cohort study which enrolled women with breast cancer (BC) attending 8 participating cancer centers in Malaysia in 2011. All patients were followed up for 12 months from diagnosis to determine their access to therapies. We assess care performance using measures developed by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comprehensive Cancer Network, American College of Surgeons' National Accreditation Program for Breast Centers as well as our local guideline.
    RESULTS: Seven hundred and fifty seven patients were included in the study; they represent about 20% of incident BC in Malaysia. Performance results were mixed. Late presentation was 40%. Access to diagnostic and breast surgery services were timely; the interval from presentation to tissue diagnosis was short (median = 9 days), and all who needed surgery could receive it with only a short wait (median = 11 days). Performance of radiation, chemo and hormonal therapy services showed that about 75 to 80% of patients could access these treatments timely, and those who could not were because they sought alternative treatment or they refused treatment. Access to Trastuzumab was limited to only 19% of eligible patients.
    CONCLUSIONS: These performance results are probably acceptable for a middle income country though far below the 95% or higher adherence rates routinely reported by centres in developed countries. High cost trastuzumab was inaccessible to this population without public funding support.
  2. Poh ME, How SH, Ho GF, Pang YK, Hasbullah HH, Tho LM, et al.
    Cancer Manag Res, 2023;15:31-41.
    PMID: 36660237 DOI: 10.2147/CMAR.S393729
    PURPOSE: Anaplastic lymphoma kinase (ALK) inhibitors are associated with good overall survival (OS) for ALK-positive metastatic non-small cell lung cancer (NSCLC). However, these treatments can be unavailable or limited by financial constraints in developing countries. Using data from a nationwide lung cancer registry, the present study aimed to identify treatment patterns and clinical outcomes of ALK-positive NSCLC in Malaysia.

    METHODS: This retrospective study examined data of patients with ALK-positive NSCLC from 18 major hospitals (public, private, or university teaching hospitals) throughout Malaysia between January 1, 2015 and December 31, 2020 from the National Cardiovascular and Thoracic Surgical Database (NCTSD). Data on baseline characteristics, treatments, radiological findings, and pathological findings were collected. Overall survival (OS) and time on treatment (TOT) were calculated using the Kaplan-Meier method.

    RESULTS: There were 1581 NSCLC patients in the NCTSD. Based on ALK gene-rearrangement test results, only 65 patients (4.1%) had ALK-positive advanced NSCLC. Of these 65 patients, 59 received standard-of-care treatment and were included in the analysis. Crizotinib was the most commonly prescribed ALK inhibitor, followed by alectinib and ceritinib. Patients on ALK inhibitors had better median OS (62 months for first-generation inhibitors, not reached at time of analysis for second-generation inhibitors) compared to chemotherapy (27 months), but this was not statistically significant (P=0.835) due to sample-size limitations. Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P<0.01).

    CONCLUSION: Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.

  3. Poh ME, Chai CS, Liam CK, Ho GF, Pang YK, Hasbullah HH, et al.
    Transl Lung Cancer Res, 2024 Feb 29;13(2):307-320.
    PMID: 38496703 DOI: 10.21037/tlcr-23-691
    BACKGROUND: Afatinib can be started at a dose lower than the recommended starting dose of 40 mg/day for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), however treatment outcomes in real-world clinical practice remains unclear.

    METHODS: This retrospective study of patients with NSCLC from 18 major hospitals (public, private or university teaching hospitals) enrolled in Malaysia's National Cardiovascular and Thoracic Surgical Database (NCTSD) assessed the efficacy of lower doses of afatinib on treatment outcomes in a real-world clinical practice. Data on clinical characteristics, afatinib dosing, and treatment outcomes for patients included in NCTSD from 1st January 2015 to 31st December 2020 were analyzed.

    RESULTS: Of the 133 patients studied, 94.7% had adenocarcinoma. Majority of the patients (60.9%) had EGFR exon 19 deletion and 23.3% had EGFR exon 21 L858R point mutation. The mean age of patients was 64.1 years and majority (83.5%) had Eastern Cooperative Oncology Group performance status of 2-4 at diagnosis. The most common afatinib starting doses were 40 mg (37.6%), 30 mg (29.3%), and 20 mg (26.3%) once daily (OD), respectively. A quarter of patients had dose reduction (23.3%) due to side effects or cost constraints. Majority of the patients had partial response to afatinib (63.2%) whilst 2.3% had complete response. Interestingly, the objective response rate was significantly higher (72.3%) with afatinib OD doses of less than 40 mg compared to 40 mg (54.0%) (P=0.032). Patients on lower doses of afatinib were two times more likely to achieve an objective response [odds ratio =2.64; 95% confidence interval (CI): 1.20-5.83; P=0.016]. These patients had a numerically but not statistically longer median time to treatment failure (TTF). Median TTF (95% CI) for the overall cohort was 12.4 (10.02-14.78) months. Median overall survival (95% CI) was 21.30 (15.86-26.75) months.

    CONCLUSIONS: Lower afatinib doses (<40 mg OD) could be equally effective as standard dose in patients with EGFR-mutant advanced NSCLC and may be more suited to Asian patients, minimizing side effects that may occur at higher dosages of afatinib leading to dose interruptions and affecting treatment outcomes.

  4. Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, et al.
    Ann Oncol, 2024 Sep 04.
    PMID: 39241963 DOI: 10.1016/j.annonc.2024.08.2344
    BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous Phase 2 trial of locally recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective anti-tumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared to conventional chemotherapy treatment.

    PATIENTS AND METHODS: This multicenter, randomized, Phase 3 trial evaluated the efficacy and safety of GC followed by EBV-CTL vs. GC alone as first-line treatment for R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the United States (US) were included. Subjects were randomized to first-line GC (4 cycles) and EBV-CTL (6 cycles) or GC (6 cycles) in a 1:1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.

    CLINICALTRIALS: gov identifier: NCT02578641.

    RESULTS: 330 subjects with NPC were enrolled. Most subjects in both treatment arms received ≥4 cycles of chemotherapy and most subjects in the GC+EBV-CTL group received ≥2 infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+EBV-CTL subjects. The median OS was 25.0 months in the GC+EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% CI: 0.91, 1.56; P = 0.194). Only 1 subject experienced a Grade 2 serious adverse event related to EBV-CTL.

    CONCLUSION: GC+EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS vs. chemotherapy. This is the largest adoptive T cell therapy trial reported in solid tumors to date.

  5. Yoon SY, Wong SW, Lim J, Ahmad S, Mariapun S, Padmanabhan H, et al.
    J Med Genet, 2022 Mar;59(3):220-229.
    PMID: 33526602 DOI: 10.1136/jmedgenet-2020-107416
    BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.

    METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.

    RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms.

    CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

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