乳腺導管原位癌俗稱零期乳腺癌，主要治療方法為保乳手術＋放療。臨床前研究結(jié)果表明，曲妥珠單抗可增強HER2陽性乳腺癌放療效果。不過，對于HER2陽性乳腺導管原位癌保乳術后放療患者，曲妥珠單抗的臨床意義尚不明確。
2021年3月19日，美國臨床腫瘤學會《臨床腫瘤學雜志》在線發(fā)表NRG（NSABP＋RTOG＋GOG）腫瘤學協(xié)作組、拉什大學、匹茲堡大學、西北大學、弗吉尼亞聯(lián)邦大學、科羅拉多大學、凱薩醫(yī)療中心、凱斯西儲大學、托馬斯杰斐遜大學、西密歇根癌癥研究聯(lián)盟、佛羅里達大學的NSABP B-43研究報告，對HER2陽性乳腺導管原位癌保乳術后全乳放療±曲妥珠單抗的同側(cè)乳腺癌復發(fā)率進行了比較。
NSABP B-43 (NCT00769379): A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy
該多中心隨機對照三期臨床研究于2008年12月10日～2014年12月8日從全國入組體力狀態(tài)評分為0或1、已知雌激素受體和/或孕激素受體狀態(tài)、集中檢測HER2為陽性的乳腺導管原位癌保乳術后患者2014例，按1∶1隨機分為兩組：全乳放療組1008例、全乳放療＋曲妥珠單抗組1006例。根據(jù)絕經(jīng)狀態(tài)、術后內(nèi)分泌治療計劃、腫瘤分級進行亞組分析。當發(fā)生同側(cè)乳腺癌復發(fā)事件163例或全部入組患者隨訪≥5年時，進行意向治療初步分析。
結(jié)果，截至2019年12月31日，中位隨訪79.2個月，同側(cè)乳腺癌復發(fā)114例，全部入組患者隨訪≥5年，全乳放療組、全乳放療＋曲妥珠單抗組分別失訪3例、13例，其余1005例全乳放療與993例全乳放療＋曲妥珠單抗的患者相比：
同側(cè)乳腺癌復發(fā)：63例比51例（風險比：0.81，95%置信區(qū)間：0.56～1.17，P=0.26）
同側(cè)浸潤癌復發(fā)：18例比20例（風險比：1.11，95%置信區(qū)間：0.59～2.10，P=0.71）
同側(cè)原位癌復發(fā)：45例比31例（風險比：0.68，95%置信區(qū)間：0.43～1.08，P=0.11）
年均同側(cè)乳腺癌復發(fā)率：0.99%比0.79%
死亡：26例比22例（風險比：0.85，P=0.59）
根據(jù)亞組分析，對于絕經(jīng)后、未計劃術后內(nèi)分泌治療、腫瘤分級較高的患者，全乳放療±曲妥珠單抗相比，同側(cè)乳腺癌復發(fā)風險較低，不過亦無統(tǒng)計學意義。
因此，該研究結(jié)果表明，對于HER2陽性乳腺導管原位癌保乳術后患者，全乳放療±曲妥珠單抗相比，同側(cè)乳腺癌復發(fā)風險減少19%，雖有臨床意義，但無統(tǒng)計學意義，故該研究結(jié)果為陰性。
J Clin Oncol. 2021 Mar 19. Online ahead of print.
Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.
Cobleigh MA, Anderson SJ, Siziopikou KP, Arthur DW, Rabinovitch R, Julian TB, Parda DS, Seaward SA, Carter DL, Lyons JA, Dillmon MS, Magrinat GC, Kavadi VS, Zibelli AM, Tiriveedhi L, Hill ML, Melnik MK, Beriwal S, Mamounas EP, Wolmark N.
NRG Oncology, Pittsburgh, PA; University of Pittsburgh, Pittsburgh, PA; Allegheny Health Network, Pittsburgh, PA; UPMC Hillman Cancer Center, Magee Womens Hospital, Pittsburgh, PA; Rush University Medical Center, Chicago, IL; Northwestern University Feinberg School of Medicine, Chicago, IL; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; University of Colorado Cancer Center, Aurora, CO; Rocky Mountain Cancer Centers, Aurora, CO; Kaiser Permanente Cancer Research Program, Vallejo, CA; US Oncology, The Woodlands, TX; University Hospitals Seidman Cancer Center, Cleveland, OH; Harbin Clinic, Rome, GA; Cone Health Center, Greensboro, NC; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; Mercy Clinic Cancer and Hematology, Springfield, MO; Mission Cancer and Blood, Des Moines, IA; Cancer Research Consortium of West Michigan, Grand Rapids, MI; Orlando Health UF Health Cancer Center, Orlando, FL.
PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS).
PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years.
RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years.
CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
PMID: 33739848
DOI: 10.1200/JCO.20.02824
