一线曲妥珠单抗至进展时间或可预测二线拉帕替尼＋卡培他滨的效果
2016年5月25日，美国《公共科学图书馆·综合》在线发表《拉帕替尼＋卡培他滨治疗HER2阳性曲妥珠单抗耐药转移性乳腺癌患者的效果预测因素：意大利回顾性多中心研究HERLAPAC结果》。
该研究从意大利13家医院收集了2007年3月～2013年12月连续148例接受拉帕替尼＋卡培他滨治疗的患者数据，采用乘积极限法获得无进展生存（PFS）和总生存（OS）并以时序检验进行比较，采用二进制逻辑回归和Cox比例风险分析临床病理学变量与结局的相关性。
经过41个月的中位随访，中位PFS和OS分别为7和21个月。PFS＞7个月的患者与PFS≤7个月的患者相比，OS较长（36比15个月，P＜0.001）。多变量分析显示拉帕替尼疗法的PFS和OS获益与一线曲妥珠单抗疗法的至进展时间（TTP）有显著相关性。尤其，一线曲妥珠单抗疗法的TTP每增加1个月，拉帕替尼疗法开始后进展和死亡的风险分别降低2%和4%。
因此，一线曲妥珠单抗的TTP较长似可预测二线拉帕替尼＋卡培他滨的PFS和OS较长。
PLoS One. 2016 May 25;11(5):e0156221.
Predictive Factors of Lapatinib and Capecitabine Activity in Patients with HER2-Positive, Trastuzumab-Resistant Metastatic Breast Cancer: Results from the Italian Retrospective Multicenter HERLAPAC Study.
Gori S, Inno A, Rossi V, Turazza M, Fiorio E, Fabi A, Bisagni G, Foglietta J, Santini D, Pavese I, Pellegrino A, Zambelli A, Vici P, Leonardi V, Barni S, Saracchini S, Bogina G, Marchetti F, Duranti S, Lunardi G, Montemurro F.
Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
Ospedale Civile di Saluzzo, Saluzzo, Italy.
AO Universitaria Integrata Verona, Verona, Italy.
INT Regina Elena, Roma, Italy.
IRCCS AO S.Maria Nuova, Reggio Emilia, Italy.
S.Maria della Misericordia Hospital, Perugia, Italy.
Università Campus Biomedico, Roma, Italy.
San Pietro Fatebenefratelli Hospital, Roma, Italy.
IRCCS Fondazione S. Maugeri, Pavia, Italy.
ARNAS Civico, Palermo, Italy.
AO Treviglio - Bergamo, Bergamo, Italy.
S.Maria degli Angeli Hospital, Pordenone, Italy.
Investigative Clinical Oncology (INCO), Fondazione del Piemonte per L'Oncologia, Candiolo Cancer Institute (IRCCS), Candiolo, Italy.
BACKGROUND: There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer.
METHODS: Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test. The association of clinicopathological variables and the outcome was studied by binary logistic regression analysis and Cox proportional hazard analysis.
RESULTS: At a median follow-up of 41 months, median PFS and OS were 7 and 21 months, respectively. Patents with a PFS longer than 7 months had a significantly longer OS, compared with patients with a PFS equal to or shorter than 7 months (36 vs 15 months; p<0.001). Multivariate analysis revealed the benefit of lapatinib-based therapy in terms of PFS and OS was significantly associated with time-to-progression (TTP) on prior first-line trastuzumab-based therapy. In particular, each additional month on first-line trastuzumab based therapy was associated with a reduction in hazard of progression and death after the initiation of lapatinib-based therapy of 2% and 4%, respectively.
CONCLUSIONS: A longer TTP to first line trastuzumab seems to predict a prolonged PFS and OS with subsequent lapatinib and capecitabine.
PMID: 27224517
DOI: 10.1371/journal.pone.0156221