Abstract P2-15-01: Impact of adjuvant trastuzumab (AT) on survival in metastatic (M1) her2 positive breast cancer
Authors: Lohrisch C , Speers C , Francl M , Tyldesley S 
Published: August 2014

Background: Recurrence rates have declined since AT was added to chemotherapy (chx) for her2+ early breast cancer (BC). This has led to under-representation of patients (pts) relapsing after AT in M1 anti-her2 therapy trials. Trastuzumab was introduced in British Columbia in 1998 for M1 disease and 2005 for adjuvant therapy (at inception, pts completing chx within 1 year prior could receive delayed AT).

Methods: We examined patterns of relapse and median survival from M1 among 3 cohorts of M1 her2+ BC: 1. de novo M1; 2. recurrence with no prior AT; 3. recurrence despite AT. Cohorts were drawn from the BCOU, which tracks outcomes for all referred pts to British Columbia Cancer Agency (BCCA) since 1989. Pts were excluded if they had a contralateral invasive BC (CLBC) within 10 years prior, or synchronous BC if one was her2-, unless M1 site was biopsied and her2+; previous (within 10 years) or synchronous other cancer; or died without BC relapse. Relapse was first ipsilateral local, regional, or distant recurrence, or death from breast cancer. Subsequent isolated CLBC was not counted as a recurrence. Last contact date was used as censoring date for survival among pts still alive on that date; date of death was recorded for deceased pts.

Cohort characteristicsCohort123 De novo M1No ATATN161192133Median RFS, diagnosis to M1, years (95% CI)02.4 (1.8, 3.0)2.5 (2.3, 2.8)*Median year of M1 (range)2006 (2000-2009)2003 (1998-2010)2010 (2004-2013)Median age at M1, years56.154.853.4% ER +/-/unknown50/45/547/47/550/50/0Disease at first relapse, n (%)CNS (symptomatic)4 (2.5)8 (4)31 (23)Liver66 (41)67 (35)37 (28)Lung45 (28)68 (35)40 (30)Bone79 (49)81 (42)50 (38)Isolated resected loco-regionalNA14 (7)9 (7)unresected loco-regionalNA32 (17)16 (12)Distant nodes39 (24)60 (31)25 (19)Other6 (4)9 (5)4 (3)CNS at any point during M163 (39)92 (48)60 (45)Current status, n (%)Dead123 (76.4)166 (86.5)99 (74.4)Lost to follow up4 (2.5)5 (2.6)2 (1.5)Median survival from M1, years (95% CI)2.8 (2.5,3.1)2.3 (1.9,2.6)1.1 (0.9,1.3)**Median follow up from M1, years (95% CI)All patients2.82.21.0Alive patients5.07.61.5CI, confidence interval. * p = 0.008, **p&lt;0.001

Results: 80% of cohort 3 and 19% of cohort 2 had adjuvant anthracycline plus taxane chx. 14 (10.5%) of cohort 3 pts relapsed while on AT. Age at M1 and% ER+ was similar in all cohorts. Cohort 3 had the lowest rate of liver and highest rate of CNS metastases at M1 presentation. CNS metastases rates over the entire M1 course was similar in all cohorts, however. Despite differences in follow up duration, survival estimates are mature, as at least 75% of pts have died. Median survival was shortest in pts relapsing after AT (p&lt;0.001) despite potential access within clinical trials to more anti-her2 therapy due to later chronologic diagnosis. Pts with denovo M1 had the longest survival despite high rates of initial liver and similar rates of CNS metastases during their M1 course.

Conclusions: AT alters the presentation and survival of M1 disease. Pts with prior AT should be screened for CNS M1 at relapse. It may be particularly important to use a combination of anti-her2 agents in pts relapsing despite AT. Future her2+ M1 trials should stratify by denovo M1 versus prior AT.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-15-01.