Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

Abstract

Background: Real-world outcomes for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab in combination with taxane chemotherapy plus trastuzumab (TaxTP) in the first line setting and trastuzumab emtansine (TE) in any line of treatment are lacking. Methods: Cohorts of patients treated with (1) TaxTP and (2) TE from January 1, 2013 through December 31, 2016 were retrospectively obtained from a population-based database. Cohorts were described according to age, hormone receptor (HR) status, prior systemic therapies, event-free survival (EFS) defined as time from start of treatment to start of next line of treatment or death, and overall survival (OS). Results: A total of 122 patients were treated with TaxTP and 104 with TE. In the TaxTP cohort, EFS was significantly longer in the trastuzumab-naïve group compared with the adjuvant trastuzumab group (median EFS = 27.0 vs 12.4 months; P = .002). In the TaxTP cohort, median OS was not reached. In the TE cohort, EFS was significantly longer in the pertuzumab-naïve group compared with pertuzumab-exposed group (median time to treatment failure [TTF] = 18.7 vs 5.5 months; P < .001). Overall survival was also significantly longer in the pertuzumab-naïve group compared with the pertuzumab-exposed group (median OS = 23.2 vs 14.1 months; P = .022). In multivariable analyses, adjuvant trastuzumab and prior pertuzumab exposure in the metastatic setting remained significant predictors of inferior EFS for patients treated with TaxTP and TE, respectively. Conclusions: New anti-HER2 therapies appear to be clinically relevant in the real-world.

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

“…The proportion of our cohort with previous (neo)adjuvant treatment with trastuzumab (48%) was also similar to that reported in other observational studies [ [19] , [20] , [21] ]. The high proportion of patients treated with first-line T-DM1 who received (neo)adjuvant trastuzumab in our cohort (81%) likely reflects Australian prescribing restrictions for T-DM1 that require patients to relapse on or within 6 months of completing adjuvant trastuzumab in order to access first-line T-DM1, and overall, T-DM1 appears to have been used largely within Australian prescribing restrictions [ 22 ].…”

“…The recent Canadian studies have reported similar OS estimates (15.4 months and 19.0 months) from their real-world cohorts to ours (18.9 months) [18,19]. Both of these studies also reported worse OS outcomes for patients who received T-DM1 following treatment with pertuzumab [18,19]. More research from patients treated in routine clinical care is needed to better understand the impact of prior pertuzumab treatment on the outcomes observed with T-DM1 therapy, but our OS estimate for second-line T-DM1 patients was more similar to that from the third-and laterline T-DM1-treated patients enrolled in the TH3RESA study (final estimate: 23 months) [28].…”

“…The proportions of patients in our cohort 65 years and older (31%) and 75 years and older (11%) were notably larger than that reported from EMILIA. Older patients represent a growing proportion of patients treated with HER2-targeted agents [17] and recent Canadian real-world cohorts (of similar size to ours) from Ontario and Alberta reported median ages closer to our cohort (56 and 58 years, respectively [18,19]).…”

Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting

“…Some studies seem to suggest lower efficacy of T-DM1 following the triplet. A recent Canadian study [23] report on 104 patients treated with T-DM1 at any line. Event Free Survival was significantly longer in the pertuzumab-naïve group compared with pertuzumab exposed group (median time to treatment failure [TTF] = 18.7 vs 5.5 months; p < .001).…”

Comparative effectiveness of trastuzumab emtansine versus lapatinib plus chemotherapy for HER2+ metastatic breast cancer

“…Previous real-world studies of T-DM1 have reported absolute estimates of effectiveness in HER2+ mBC patients treated with T-DM1 and have provided comparisons of T-DM1 effectiveness between T-DM1 patients treated with different prior treatment regimens or with differing severity of disease [4][5][6][7][8][9], our study provides estimates of absolute effectiveness of T-DM1 in a larger cohort of second-line mBC patients than observed in any of these studies. Further, while these studies focused on absolute effectiveness, to our knowledge ours is the first to report on the real-world effectiveness of T-DM1 in second-line mBC relative to an alternative treatment option in this setting.…”