Abstract P4-21-07: Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy in patients ≥65 years with HER2-positive locally recurrent/metastatic breast cancer: Subgroup analyses of the PERUSE study
Authors: Miles D , Schneeweiss A , Peretz-Yablonski T , Ciruelos E , Puglisi F , Easton V , Lindegger N , Restuccia E , Bachelot T 
Published: March 2017

Abstract
Background:
First-line (1L) docetaxel+trastuzumab+pertuzumab (THP) is approved for HER2-positive metastatic breast cancer (MBC), based on superior progression-free (PFS) and overall survival vs TH in the phase III CLEOPATRA trial. Predefined CLEOPATRA subgroup analyses suggested that THP use should not be limited by patient (pt) age: toxicity was increased but efficacy was similar in pts ≥65 vs &lt;65 years. PERUSE (NCT01572038) examined investigator's choice of taxane+HP for HER2-positive locally recurrent (LR)/MBC. We report preliminary safety and efficacy in pts ≥65 and &lt;65 years.
Methods:
In this multicentre, single-arm phase IIIb study, pts with ECOG PS ≤2 and no prior systemic therapy for LR/MBC (except endocrine therapy) receive investigator's choice of T, paclitaxel (PAC), or nab-PAC + H (8→6 mg/kg q3w) + P (840→420 mg q3w) until disease progression/unacceptable toxicity. The primary endpoint is safety. Secondary endpoints include PFS, estimated using the Kaplan–Meier method.
Results:
At data cutoff (1 Apr 2016), 1436 pts were included in the safety/ITT populations. 312 pts (22%) were aged ≥65 at study entry; they were more likely to have comorbidities than the &lt;65 group (91% vs 69%, including vascular disorders [56% vs 22%]; most commonly hypertension [51% vs 17%]) and be ECOG PS 1–2 (50% vs 38%).
Proportions of pts with visceral and hormone receptor-positive disease were similar (78% vs 74% and 65% vs 64%, respectively).
Median duration of chemotherapy was similar but median exposure to antibodies was shorter in the ≥65 vs &lt;65 group: H 11.7 mo (range &lt;1–45.8) vs 17.5 mo (&lt;1–45.9); P 11.6 mo (&lt;1–45.8) vs 17.8 mo (&lt;1–45.9).
Interruptions/discontinuations due to treatment-emergent adverse events (TEAEs) were more common in pts ≥65 compared with pts &lt;65 with respect to taxanes (50% vs 35%), H (41% vs 26%), and P (38% vs 23%).
TEAEs related to taxanes, H, and P were generally similar in pts aged ≥65 and &lt;65 (93% each, 67% vs 62%, and 71% vs 70%, respectively).
Serious TEAE rates and most common grade ≥3 TEAEs of interest are shown in table 1.
Table 1Pts, n (%) &lt;65 ≥65 n=1124 n=312 TPACNab-PACTPACNab-PAC n=638n=431n=51n=137n=158n=14Serious223 (35)124 (29)18 (35)59 (43)61 (39)3 (21)Grade ≥3 Neutropenia88 (14)18 (4)1 (2)22 (16)13 (8)0Diarrhea45 (7)33 (8)3 (6)17 (12)17 (11)1 (7)Febrile neutropenia67 (11)5 (1)014 (10)2 (1)0Fatigue19 (3)3 (1)1 (2)2 (1)7 (4)0Asthenia9 (1)2 (&lt;1)07 (5)8 (5)0Peripheral neuropathy8 (1)8 (2)02 (1)7 (4)0Anemia9 (1)4 (1)1 (2)2 (1)8 (5)1 (7)Left ventricular dysfunction05 (1)01 (1)4 (3)1 (7)
Preliminary median PFS at the time of this analysis was 23.2 mo in the &lt;65 group (95% CI 20.7–25.3; median follow-up 18 mo) and 14.7 mo in the ≥65 group (95% CI 12.8–20.2; median follow-up 14 mo); 511/1124 (45%) and 116/312 (37%) pts were censored, respectively.
Conclusion:
Preliminary findings with 1L taxane+HP in this large cohort of LR/MBC pts show that pts aged ≥65 years had more comorbidities and poorer PS at study entry compared with those aged &lt;65, and that serious TEAEs were noted more frequently. Treatment exposure and PFS were shorter for pts aged ≥65.
Citation Format: Miles D, Schneeweiss A, Peretz-Yablonski T, Ciruelos E, Puglisi F, Easton V, Lindegger N, Restuccia E, Bachelot T. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy in patients ≥65 years with HER2-positive locally recurrent/metastatic breast cancer: Subgroup analyses of the PERUSE study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-07.