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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e19385-e19385
    Abstract: e19385 Background: Pembrolizumab has dramatically improved the survival of patients with non-small cell lung cancer (NSCLC) and is considered the standard of care for first line treatment of NSCLC who do not harbour oncogenic drivers. The fixed dose of 200mg was approved by the US Food and Drug Administration. The dose of 200mg was based on pharmacokinetic analysis. Studies have demonstrated equivalent efficacy with weight-based dosing 2mg/kg. An average Asian weighs 50-60kg. We aimed to look at the efficacy of pembrolizumab at a low fixed dose compared to the standard dosing. Methods: A review of all consecutive patients receiving pembrolizumab for advanced NSCLC from January 2016 to December 2019 in a large, high-volume academic medical centre, the National University Hospital, Singapore was conducted. Data fields collected include patient’s demographics, treatment doses and clinical characteristics. Time on treatment and overall survival were analysed using the Kaplan Meier method. Results: In total, 92 ECOG 0-2 patients with advanced NSCLC were treated with pembrolizumab. Median age was 69 years (Range, 29-92). Most were males (76%) and Chinese race (68%). Of the 92 patients, 46 (50%) and 46 (50%) received 100mg (Pem100) and 200mg (Pem200) of pembrolizumab respectively. Pembrolizumab was prescribed as first line in 73 (79%) and second line in 19 patients (21%). The average dose of pembrolizumab received in the low dose group was 1.87mg/kg (Range, 1.24mg/kg – 2.70mg/kg). 88 patients were included in the survival analysis. 4 were excluded due to the presence of an oncogenic driver. Patients were followed up for a median of 13.2 months. There was no difference in progression free survival between Pem100 and Pem200 for first-line single agent and when combined with chemotherapy (PFS: NR versus 5.3months, HR 2.17, 95% CI 0.76-6.16, p = 0.15 and NR vs 16.9 months, HR 2.89, 95% CI 0.35-25.16, p = 0.33 respectively). For patients who received pembrolizumab in the first line setting, the response rate was 56% vs 20% (p = 0.07), 67% vs 52% (p = 0.69) for Pem100 and Pem200 as a single agent and when combined with chemotherapy respectively. The median number of cycles received was 8.9 (Range, 1-60 cycles), translating to estimated cost savings of SGD 45 395 (~ USD 32 664) per patient who received Pem100. Conclusions: A lower fixed dose of pembrolizumab at 100mg showed no difference in progression free survival and response rate in an Asian cohort with significant cost savings. A further randomised controlled trial in an Asian population should be carried out.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3584-3584
    Abstract: 3584 Background: Trifluridine/tipiracil (TAS-102) is currently approved as third-line treatment in metastatic colorectal cancer (mCRC). However, there is paucity of real-world data on the tolerability and efficacy with biweekly dosing as monotherapy or in combination with bevacizumab. In this study, we present our center’s experience with biweekly TAS-102 with or without bevacizumab in mCRC patients (pts). Methods: We performed a single center retrospective observational study of pts receiving TAS-102 between 2018 and 2021. Results: A total of 83 pts were included (53 men, 30 women), with a median age of 64 years. Majority of pts were treated with TAS-102 in the 3rd-line (48.2%) and 4th-line (28.9%) setting. Almost all (94.0%) were of ECOG ≤ 1 at the initiation of treatment. The mean number of cycles administered was 3.8 and bevacizumab (5mg/kg on Day 1, every 2 weeks) was used in combination with TAS-102 in 18 pts (21.7%). Majority of pts (84.3%) were given TAS-102 using the biweekly regimen (35mg/m2 BD, on Day 1-5 and 15-19, q28 days) rather than standard regimen (35mg/m2 BD, on Day 1-5 and 8-12, q28 days) following a change in institutional practice. Fifteen pts (18.1%) had their initial dose reduced to 30mg/m2 BD at prescriber's discretion. Median PFS and OS were 2.37 and 10.15 months, respectively. In terms of tolerability, fatigue (any grade, 42.2%) and neutropenia (any grade, 44.6%) were the two most common adverse events reported. Grade 3 or higher neutropenia and febrile neutropenia were 16.9% and 3.6%, respectively. Dose reduction during treatment was required in 15 pts (18.1%), dose delay in 31 pts (37.3%) and six pts (7.2%) discontinued treatment due to toxicity. More than half (54.2%) had at least an additional line of therapy (regorafenib, clinical trials or re-challenge previous chemotherapy agents) following disease progression with TAS-102. Conclusions: We report the largest real-world experience with biweekly TAS-102. Our pts treated with TAS-102 had comparable median PFS to the RECOURSE cohort but with significantly better OS as more than half continued to receive treatment. Biweekly dosing of TAS-102 with or without bevacizumab is well tolerated with significantly lower rates of Grade 3 neutropenia compared to the published data in the literature.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16623-e16623
    Abstract: e16623 Background: The management of aHCC has evolved dramatically in recent years, with new agents like immunotherapy receiving regulatory approval. As we begin incorporating these drugs into routine clinical practice, data on real-world sequencing of therapies and clinical outcomes are needed. Methods: We utilised the DISCOVERYAI platform, a virtual machine containing de-identified patient electronic health records to review HCC patients treated at the National University Health System, Singapore from January 2015 to December 2019. We then identified those who received systemic therapy and correlated their clinical outcomes. Results: In total, 395 HCC patients were identified; 75 received surgery, 174 received loco-regional therapy and 102 referred for consideration of systemic therapy. Of those considered for systemic therapy, median age was 65 years (range 23-87); 88% male (n = 90); hepatitis B/hepatitis C/non-hepatitis, 41(40.2%)/ 10(9.8%)/ 51(50.0%). 75.5% (n = 77) of them received systemic therapy with a TKI and/or immunotherapy. 39% (n = 30) of these received second-line treatment. Child-Pugh score at start of treatment was A5/A6/B7/B8, 38(49.3%)/ 32(41.6%)/ 5(6.5%)/ 2(2.6%) respectively. In the first-line, 66% (n = 51) received TKI and 34% (n = 26) received immunotherapy. Amongst those treated with first-line TKI, 45% (n = 23) received second-line therapy; 65% (n = 15) immunotherapy, 35% (n = 8) another TKI. Of those treated with first-line immunotherapy, 27% (n = 7) received second-line TKI. At a median follow-up of 35 months, first-line median progression-free survival (mPFS) for TKI vs immunotherapy was 3.7 vs 3.1 months (HR 0.73; 95% CI, 0.40-1.33; p = 0.31). mPFS for second-line immunotherapy vs TKI was 4.0 vs 2.9 months (HR 0.43; 95% CI, 0.19-0.96; p = 0.04). When comparing sequencing of therapies, the combined first and second mPFS for TKI-immunotherapy/TKI-TKI/immunotherapy-TKI is 9.5/7.6/7.6 months respectively (log-rank test, p = 0.71). Those patients that received both immunotherapy and TKI had significantly higher overall survival (OS) compared to those receiving only immunotherapy or only TKI or none (mOS NR vs 10.1 vs 13.2 vs 4.7 months; p 〈 0.001). Conclusions: TKI remains an important pillar of treatment in aHCC in the era of immunotherapy. While immunotherapy provides long durable responses and benefit in a minority of patients, the majority appear to benefit from TKI. Biomarker studies are needed to discern treatment algorithms for aHCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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