Abstract P5-19-21: TRASTYVERE study: A retrospective analysis of HER2-positive metastatic breast cancer (MBC) patients treated in Spain with lapatinib (L) plus trastuzumab (T)
Authors: Gavilá Joaquin , Bermejo Begoña , Rodríguez-Lescure Álvaro , Lao Romera Juan , Manso Luis , Brunet Joan , Muñoz Eva , Santisteban Marta , Rodríguez César A , Santaballa Ana , de la Haba Juan , Sánchez-Rovira Pedro , Ruiz-Borrego Manuel , García-Saenz Jose Ángel , Cortés Javier , Llombart Antonio 
Published: May 2015

Abstract
Background: Vertical dual blockade with L and T in heavily pretreated HER2+ MBC patients has shown consistent survival gain in a phase III trial (Blackwell KL et al. 2012), justifying an EMA approval for the hormone-negative subgroup. However, there is very limited information about the futility of the combination in clinical practice, mostly in patients progressing also on prior L regimens.
Methods: We conducted a retrospective analysis among patients treated in Spain by compassionate uses for the combination of T-L. The study was approved by the regulatory authorities and ethics committees from the 14 participating centers. Major inclusion criteria were (1) HER2+ MBC; (2) progression on at least one prior line of T for advanced disease; and (3) T-L treatment started between JAN/2005 and DEC/2012. Concomitant endocrine therapy for HR+ patients as well as prior exposure to L was allowed. Chemotherapy combinations were excluded. A total of 111 patients were predefined for the primary outcome: clinical benefit rate (CBR). Secondary endpoints included time to progression (TTP), overall survival (OS) and toxicity. 114 women were included and externally monitored.
Results: The median age was 60 years (34 - 89); 64% HR+; 77% visceral disease; 32% CNS disease (37 patients); 47% with ≥3 organs involved. Mean number of prior T lines 4 (range 0-13); 64% previously treated with L. A total of 40 patients (35%) achieved a CBR (95%CI 26–44%); 6 CR, 19 PR and 15 SD lasting &gt;24 weeks. The median time to progression was 3.8 months (95%CI 3.3–5.1) and the median overall survival 21.6 months (95%CI 17.1–27.3). CBR, median TTP and median OS achieved in patients with CNS disease were 32.4% (95%CI 17.3–47.5%), 3.6 (95%CI 2.8–5.9) and 15.4 (95%CI 10.9–27.3) months, respectively.
The CBR was independent of L treatment (41.5% L naïve vs. 31.5% L pretreated, p=0.285) and HR status (39% HR- vs. 32.9% HR+, p=0.509). Patients with &lt;3 metastatic sites showed higher CBR than patients with ≥3 (45 vs. 24.1%, respectively, p=0.019). No significant trends were observed in any pre-specified condition for TTP and OS. Grade 3/4 toxicities were reported in 20 patients (17.5%). Only 2 patients report asymptomatic cardiac toxicities.
Conclusions: The combination of T-L seems safe and active in heavily pretreated patients. The combination remains active among patients progressing on prior L. Future research may focus on the ability of endocrine therapy to increase activity among HER2+/HR+ patients.
REFERENCES:
1 Blackwell KL, Burstein HJ, Storniolo AM, et al: Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 2012;30(21):2585-2592.
Citation Format: Joaquin Gavilá, Begoña Bermejo, Álvaro Rodríguez-Lescure, Juan Lao Romera, Luis Manso, Joan Brunet, Eva Muñoz, Marta Santisteban, César A Rodríguez, Ana Santaballa, Juan de la Haba, Pedro Sánchez-Rovira, Manuel Ruiz-Borrego, Jose Ángel García-Saenz, Javier Cortés, Antonio Llombart. TRASTYVERE study: A retrospective analysis of HER2-positive metastatic breast cancer (MBC) patients treated in Spain with lapatinib (L) plus trastuzumab (T) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-21.