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在印度南部资源有限的环境中,使用低剂量拉帕替尼治疗人表皮生长因子受体2(Her2)阳性转移性乳腺癌:一项回顾性审计。

Her2 positive metastatic breast cancer treated with low dose lapatinib in a resource-constrained setting in South India: a retrospective audit.

作者信息

Mathew Sherin P, Avaronnan Manuprasad, Devi Nandini, Praveen Kumar Shenoy V P

机构信息

Department of Medical Oncology, Regional Cancer Centre, Trivandrum, Kerala 695011, India.

Department of Medical Oncology, Aster MIMS, Kannur, Kerala 670621, India.

出版信息

Ecancermedicalscience. 2024 Sep 6;18:1758. doi: 10.3332/ecancer.2024.1758. eCollection 2024.

Abstract

Despite the development of newer anti-Her2 agents, access to these medicines is still restricted with lapatinib being widely used as a second-line agent in Her2-positive metastatic breast cancer. However, lapatinib at approved doses of 1,250 to 1,500 mg/day contributes to a high pill burden and financial toxicity. In a population that has an average national per capita income of only USD 2238.1, lapatinib alone contributes to a financial burden of USD 6153.56 per year (approximately USD 500 per month). A concept of 'value meal' has been suggested - the higher bioavailability of lapatinib with the meal being exploited to reduce its administered dose. This concept was utilised in a resource-constrained tertiary care center in South India and we report the outcomes. In our institution, consecutive patients with Her2 positive metastatic breast cancer from 1 January 2014 to 31 December 2020 who could not afford trastuzumab, lapatinib or any other anti-Her2 agent were offered low-dose lapatinib, 500 mg daily with meal. We conducted a retrospective cohort study of the safety and efficacy of this regimen. Among the 47 patients who received low-dose lapatinib, the majority had de novo metastatic disease (57.4%) and multiple visceral metastases (48.9%). The median number of lines of treatment before lapatinib was one. The disease control rate with lapatinib was 61.7%. The median progression-free survival was 7 months (95% CI: 5.6-8.4 months). The median duration of response was 4.5 months, ranging from 1.3 to 45.8 months. Only eleven patients (23.4%) experienced toxicity, mainly dermatological, with grade 3 in only one (2.1%) and no grade 4 toxicities. Low-dose lapatinib is a regimen that offers an acceptable disease control rate. This strategy requires further exploration, particularly for the benefit of resource-limited areas.

摘要

尽管新型抗人表皮生长因子受体2(Her2)药物不断涌现,但这些药物的可及性仍然受限,拉帕替尼在Her2阳性转移性乳腺癌中被广泛用作二线药物。然而,拉帕替尼批准剂量为每日1250至1500毫克,会带来较高的服药负担和经济毒性。在一个人均国民收入仅为2238.1美元的人群中,仅拉帕替尼一项每年就造成6153.56美元的经济负担(约合每月500美元)。有人提出了“超值套餐”的概念——利用进餐时拉帕替尼更高的生物利用度来降低给药剂量。这一概念在印度南部一家资源有限的三级医疗中心得到应用,我们在此报告相关结果。在我们机构,2014年1月1日至2020年12月31日期间连续收治的Her2阳性转移性乳腺癌患者,若无力承担曲妥珠单抗、拉帕替尼或任何其他抗Her2药物,会给予低剂量拉帕替尼,每日500毫克,进餐时服用。我们对该治疗方案的安全性和疗效进行了一项回顾性队列研究。在47例接受低剂量拉帕替尼治疗的患者中,大多数为初发转移性疾病(57.4%)且有多处内脏转移(48.9%)。接受拉帕替尼治疗前的中位治疗线数为1。拉帕替尼的疾病控制率为61.7%。中位无进展生存期为7个月(95%置信区间:5.6 - 8.4个月)。中位缓解持续时间为4.5个月,范围为1.3至45.8个月。只有11例患者(23.4%)出现毒性反应,主要为皮肤毒性,3级毒性仅1例(2.1%),无4级毒性反应。低剂量拉帕替尼治疗方案能提供可接受的疾病控制率。这一策略需要进一步探索,特别是为了资源有限地区的患者受益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/11489105/bf98e79f4d7f/can-18-1758fig1.jpg

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