Abstract P2-17-01: Overall survival (OS) in the IMELDA randomized phase III trial of maintenance bevacizumab (BEV) with or without capecitabine (CAP) for HER2-negative metastatic breast cancer (mBC)
Authors: Gligorov Joseph , Bines Jose , Alba Emilio , Mustacchi Giorgio , Cinieri Saverio , Gupta Vineet , Pierga Jean-Yves , Bozcuk Hakan , Gaafar Rabab , Gupta Sudeep , Lopez Vivanco Guillermo , Wang Xiaojia , Costa Romulo , Altundag Kadri , Chmielowska Ewa , de Ducla Sabine , Freudensprung Ulrich , Cortes Paulo , Doval Dinesh 
Published: May 2015

Abstract
BACKGROUND The open-label randomized phase III IMELDA trial demonstrated that adding CAP to maintenance BEV until disease progression (PD) after initial BEV–docetaxel (DOC) provides statistically significant and clinically meaningful improvements in both progression-free survival (PFS [primary endpoint]; hazard ratio [HR] 0.38 [95% CI 0.27–0.55]; log-rank p&lt;0.001) and OS. We present OS in subgroups representing stratification factors and clinically important populations.
METHODS Patients (pts) with HER2-negative measurable mBC, ECOG PS &lt;2, and no prior chemotherapy for mBC were eligible. After 3–6 cycles of BEV–DOC, pts without PD were randomized to BEV alone or BEV–CAP (BEV 15 mg/kg q3w; CAP 1000 mg/m2 bid d1–14 q3w) until PD. Stratification factors were estrogen receptor (ER) status, visceral metastases, response status, and lactate dehydrogenase (LDH) concentration. OS from randomization was a secondary endpoint. The planned sample size of 360 enrolled pts (290 randomized) was calculated assuming a PFS HR of 0.70 (median PFS 5.8→8.3 months) with 80% power at 2-sided α=0.05 after 244 PFS events. Recruitment was stopped prematurely after regulatory withdrawal of the BEV–DOC combination but pts who had already been enrolled and randomized were followed as originally planned.
RESULTS Between Jun 2009 and Mar 2011, 284 pts were enrolled and treated. Of these, 99 were not eligible for randomization (most commonly due to PD [41%] or AEs/toxicity [31%]) and 185 (65%) were randomized. At the time of the primary PFS analysis, representing study closure, median follow-up (from randomization) was 31.6 months. Median OS from randomization was 23.7 months in the BEV arm and 39.0 months in the BEV–CAP arm (events in 36% of pts). The HR for OS in the two randomized arms showed consistency between subgroups, favoring the BEV–CAP arm in all subgroups analyzed.
SubgroupNo. of events/No. of pts (%)Unstratified HR (95% CI)1-y OS rate (%) BEVBEV–CAP BEVBEV–CAPAll53/94 (56)33/91 (36)0.43 (0.26-0.69)a7290&lt;65 y46/81 (57)27/77 (35)0.51 (0.32-0.82)7293≥65 y7/13 (54)6/14 (43)0.50 (0.16-1.60)6879Triple negative16/21 (76)10/25 (40)0.44 (0.19-0.99)6290Hormone receptor positive37/73 (51)23/66 (35)0.53 (0.31-0.89)7591ER positiveb36/69 (52)23/64 (364)0.53 (0.32-0.90)7590ER negativeb17/25 (68)10/27 (37)0.44 (0.20-0.99)6491&lt;3 metastatic organ sites17/40 (43)17/48 (35)0.75 (0.38-1.49)8193≥3 metastatic organ sites36/54 (67)16/43 (37)0.39 (0.22-0.71)6588Visceral metastasesb38/65 (58)23/62 (37)0.43 (0.26-0.73)7092No visceral metastasesb15/29 (52)10/29 (34)0.76 (0.34-1.70)7688Complete or partial responseb36/68 (53)24/68 (35)0.61 (0.37-1.03)7389Stable diseaseb14/22 (64)6/20 (30)0.22 (0.08-0.63)68100Non-measurableb3/4 (75)3/3 (100)0.30 (0.03-2.98)6767LDH ≤1.5×ULNb50/89 (56)30/85 (35)0.49 (0.31-0.76)7294LDH &gt;1.5×ULNb3/5 (60)3/6 (50)1.01 (0.20-5.00)6044aStratified analysis. bStratification factor.
CONCLUSIONS. Combining maintenance BEV with CAP until PD after initial BEV–DOC for mBC provides a statistically significant and clinically meaningful improvement in OS (secondary endpoint), seen consistently irrespective of baseline characteristics.
Citation Format: Joseph Gligorov, Jose Bines, Emilio Alba, Giorgio Mustacchi, Saverio Cinieri, Vineet Gupta, Jean-Yves Pierga, Hakan Bozcuk, Rabab Gaafar, Sudeep Gupta, Guillermo Lopez Vivanco, Xiaojia Wang, Romulo Costa, Kadri Altundag, Ewa Chmielowska, Sabine de Ducla, Ulrich Freudensprung, Paulo Cortes, Dinesh Doval. Overall survival (OS) in the IMELDA randomized phase III trial of maintenance bevacizumab (BEV) with or without capecitabine (CAP) for HER2-negative metastatic breast cancer (mBC) [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 P2-17-01.