AZ晚期乳癌藥Lynparza 早期患者也有效

「新英格蘭醫學」(New England Journal of Medicine)網路期刊和美國臨床腫瘤醫學會(American Society of Clinical Oncology)發表的一項跨國研究發現，英國藥廠阿斯特捷利康公司 (AstraZeneca PLC) 與美國藥廠默克公司 (Merck & Co.) 銷售的藥物Lynparza，可減少早期具侵襲性乳癌女性患者的癌症復發機率。

這項長期研究是遺傳性癌症治療的最新發展，為人類對抗遺傳性乳癌增添生力軍；也證明製藥業花在新型藥物PARP抑製劑方面的昂貴投資，是值得的。

Lynparza藥在美國定價為每位患者每月1萬4449元，是阿斯特捷利康公司最暢銷產品之一，主要用於治療晚期BRCA基因突變乳癌；去年銷售額達18億元。其競爭對手葛蘭素史克(GlaxoSmithKline)2019年斥資逾50億元收購另一款PARP抑製劑Tesaro製藥廠。

阿斯特捷利康癌症部門執行副總裁弗雷德里克森(David Fredrickson)表示，阿斯特捷利康將把研究數據提交監管機構，請求批准將Lynparza用於早期BRCA基因突變乳癌治療。

PARP抑製劑的作用是截斷癌細胞修復自身DNA能力，並導致癌細胞死亡。近年來，衛生監管機構已批准此類藥物用於治療卵巢癌、乳癌、前列腺癌和胰腺癌。目前發現這些藥物對BRCA1和BRCA2基因突變癌症，特別有用。

有BRCA基因突變的女性，罹患乳癌風險更高且通常更年輕。基因突變約占美國每年確診28萬1000椿乳癌病例的5%。根據美國癌症協會數據，乳癌是女性罹癌死亡第二大原因，每年在美國造成約4萬3600人死亡。美國食品藥物管理局(FDA)已在2018年批准使用Lynparza治療晚期的BRCA基因突變乳癌。

治療3年 近86%未復發
此項研究從2014年開始，在美國和其他22個國家/地區有1836名罹患早期BRCA1或 BRCA2乳癌的女性，在參加研究前均接受過切除腫瘤手術，並在手術前後接受防止腫瘤復發的化療。根據腫瘤大小或存在於淋巴結的癌症情況，她們的復發風險都很高。

研究隨機分配一半女性每天服用Lynparza藥劑一年，另一半服用安慰劑；研究人員發現，治療開始後2年半的中位隨訪期內，與安慰劑相比，Lynparza降低了42%癌症復發或任何原因死亡的綜合風險。治療三年後，接受Lynparza治療的女性85.9%沒有復發，接受安慰劑的女性77.1%未復發。

以上文章內容摘自世界新聞網。www.worldjournal.com/wj/story/121187/5511226

Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

Abstract
BACKGROUND
Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer.

METHODS
We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease–free survival.

RESULTS
A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest.

CONCLUSIONS
Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823. opens in new tab.)

原文出處：NEJM(​www.nejm.org/doi/full/10.1056/NEJMoa21052155)