Pertuzumab (P) as ≥ second-line therapy for HER2-positive metastatic breast cancer (mBC): Swiss clinical experience
Authors: E.M. Biskup, C. Montavon Sartorius, A. Müller, C. Leo, C. Uhlmann Nussbaum, D. Koychev, A. Schreiber, C. Taverna, D. Thorn, M. Vetter
Journal: Annals of Oncology (2019)

Background: P is approved in the EU and US as 1st-line therapy in combination with docetaxel and trastuzumab (H) for HER2-positive mBC based on phase III results (CLEOPATRA). Data in later lines are very limited. In Switzerland, national regulations allow physicians to use P in this setting. We identified P-naïve patients (pts) treated with ≥2nd-line P+H in Switzerland to gain insight on clinical outcomes with P beyond 1st line. Methods: Physicians from major Swiss oncology centres retrospectively completed a questionnaire for each pt providing data on treatment details, safety and survival. Results: The analysis included 35 pts with HER2-positive mBC. Most pts (95%) had invasive ductal carcinoma, 69% had oestrogen- and/or progesterone receptor-positive tumours, 49% were stage IV at 1st diagnosis and half had received prior H. Median age was 49 (range 35–87) years. The most common metastatic sites were bone (64%), liver (43%) and lymph nodes (43%). Analysis of the earliest line of P is shown below.Table177PTreatmentTreatment lineAll pts2nd3rd≥4th(n = 14)(n = 6)(n = 15)(n = 35)P + H + chemotherapy, n (%)12 (86)5 (83)12 (80)29 (83)Taxane8 (57)4 (67)7 (47)19 (54)Vinorelbine3 (21)1 (17)2 (13)6 (17)Gemcitabine001 (7)1 (3)Carboplatin001 (7)1 (3)Anthracycline1 (7)01 (7)2 (6)P + H + endocrine therapy, n (%)1 (7)001 (3)P + H, n (%)1 (7)1 (17)3 (20)5 (14)Median P duration (range), months6 (2–30)6 (2–60)11 (2–40)6 (2–60)Reason for stopping treatment, n (%)Disease progression10 (71)4 (67)9 (60)23 (66)Toxicity2 (14)1 (17)2 (13)5 (14)Missing1 (7)1 (17)2 (13)4 (11)Ongoing1 (7)02 (13)3 (9)Grade (G) 3/4 adverse events (AEs) were reported in 14% of pts. Only 1 pt discontinued therapy because of P-related toxicity. The most common AE (irrespective of cause) was fatigue (all-G 46% of pts; G3 11%). Congestive heart disease occurred in 14% (6% G3), nausea in 14% (all G1), myelosuppression in 12% (6% G3), diarrhoea in 9% (all G1) and vomiting and mucositis each in 3% (G2). By 12 Sep 2017, 20 pts (57%) had died. Median overall survival was 6.2 (95% CI 3.9–11.6) years. Open table in a new tab Grade (G) 3/4 adverse events (AEs) were reported in 14% of pts. Only 1 pt discontinued therapy because of P-related toxicity. The most common AE (irrespective of cause) was fatigue (all-G 46% of pts; G3 11%). Congestive heart disease occurred in 14% (6% G3), nausea in 14% (all G1), myelosuppression in 12% (6% G3), diarrhoea in 9% (all G1) and vomiting and mucositis each in 3% (G2). By 12 Sep 2017, 20 pts (57%) had died. Median overall survival was 6.2 (95% CI 3.9–11.6) years. Conclusions: In this small retrospective analysis, median overall survival was similar to that reported with 1st-line P in CLEOPATRA. Diarrhoea was generally unproblematic and low grade; cardiac safety was as expected. These data support P in later lines if not used in the 1st line. Editorial acknowledgement: Jennifer Kelly (Medi-Kelsey Ltd), funded by Roche Pharma (Schweiz) AG. Legal entity responsible for the study: Dr Biskup and Dr Vetter. Funding: Roche Pharma (Switzerland) provided administrative support for this analysis. Disclosure: A. Müller: Honoraria: Roche Switzerland, Novartis, Pfizer, Amgen, Tesaro; Consulting/advisory role: Roche Switzerland, Novartis, AstraZeneca, Pfizer, Amgen; Expert testimony: Roche Switzerland; Travel/accommodation expenses: Roche, AstraZeneca, Pfizer, Novartis. C. Leo: Honoraria: Pfizer, AstraZeneca; Consulting/advisory role: Pfizer, AstraZeneca; Travel/accommodation expenses: Roche. C. Uhlmann Nussbaum: Stock: Roche; Consulting/advisory role: Sanofi, Boehringer Ingelheim, Roche. D. Koychev: Consulting/advisory role: Roche, Novartis, Takeda, Pfizer; Travel/accommodation expenses: Novartis, Roche, Takeda. A. Schreiber: Honoraria: Amgen, Roche, Pfizer, MSD, BMS, Lilly, Celgene, Merck; Travel/accommodation expenses: Amgen, Roche, Pfizer, MSD, BMS, Lilly, Celgene, Merck. C. Taverna: Consulting/advisory role: Celgene, Amgen, Janssen; Research funding: Celgene. D. Thorn: Honoraria: Roche; Consulting/advisory role: Roche; Travel/accommodation expenses: Roche, Amgen, Teva, Novartis, Celgene. M. Vetter: Employment: Roche (family member); Honoraria: Roche, Novartis, Pfizer; Consulting/advisory role: Roche, Novartis, Pfizer; Research funding: Roche. All other authors have declared no conflicts of interest.