Human epidermal growth factor receptor 2 dual blockade with trastuzumab and pertuzumab in real life: Italian clinical practice versus the CLEOPATRA trial results

Placido, Sabino De; Giuliano, Mario; Schettini, Francesco; Arx, Claudia von; Buono, Giuseppe; Riccardi, Ferdinando; Cianniello, Daniela; Caputo, Roberta; Puglisi, Fabio; Bonotto, Marta; Fabi, Alessandra; Bilancia, Domenico; Ciccarese, Mariangela; Lorusso, Vito; Michelotti, Andrea; Bruzzese, Dario; Veneziani, Bianca Maria; Locci, Mariavittoria; Laurentiis, Michelino De; Arpino, Grazia

doi:10.1016/j.breast.2017.12.012

Cited by 32 publications

(44 citation statements)

References 21 publications

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“…PERUSE findings complement results from the CLEOPATRA trial, indicating that findings from a phase III trial can be replicated in the routine clinical practice setting. The results also expand upon recently published retrospective and real-world studies of patients treated with pertuzumab, trastuzumab and the investigator's chosen taxane in the United States, Italy and Turkey, which reported median PFS ranging from 17 to 29 months [14][15][16][17]. Strengths of PERUSE results compared with previous reports include the prospective nature of the study, the larger proportion of patients treated with paclitaxel instead of docetaxel, the more rigorous data collection and the regular schedule of tumour assessment according to RECIST (version 1.1).…”

Section: Discussionsupporting

confidence: 79%

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Bachelot¹,

Ciruelos²,

Schneeweiß³

et al. 2019

Annals of Oncology

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See Appendix for individual names.Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods:In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results:Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.ClinicalTrials.gov: NCT01572038.

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Section: Discussionsupporting

confidence: 79%

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Bachelot¹,

Ciruelos²,

Schneeweiß³

et al. 2019

Annals of Oncology

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“…Likewise, the rate of dose reduction for docetaxel in Italian study was found in a higher rate (85%) than that in the CLEOPATRA study, indicating similar ratios to our real life data. However, unlike our analysis, the median cycle number of pertuzumab + trastuzumab combination (with or without docetaxel) was 8 (17). When considering the side-effect profile, it was observed that there were differences in the frequency of side-effects in our study compared to those reported in phase III clinical study and other retrospective studies.…”

Section: Discussioncontrasting

confidence: 86%

“…As compared with literature, hematological side effects in our study were observed to be relatively at low rates, with 3 (10.7%) of the patients experiencing grade 1 thrombocytopenia compared to 25 (7.8%) of those in the study by Esin et al, with only 3 of them being grade 3-4 (19). In our study, neutropenia was seen in 8 (28.6%) patients, with 3 of them being grade 1-2 (10.7%), 4 (14%) grade 3, and 1 (3.6%) grade 4 versus 215 (52.8%) patients in CLEOPATRA trial, and 23 (15%) patients in Italian study (17). Robert et al reported the incidence of neutropenia and neutropenic fever in their study as 24.9% and 2.3%, respectively (18) compared to 35.7% and 4.1% in the retrospective study by Esin et al (19).…”

Section: Discussionsupporting

confidence: 49%

“…To illustrate, in the CLEOPATRA study, diarrhea was the most common side effect, with a rate of 66.8% compared to 14.3% in our study. The most frequent side effects in our study were fatigue and arthralgia/myalgia, with the rates of 75% and 64.3, respectively compared to 37.6% and 15% in CLEOPATRA, 26% and 6% in a retrospective analysis by Placido et al, respectively (12,17). In our study, neuropathy occurred in 8 (28.6%) patients, with the 5 (17.8%) of them being grade 3 compared to 11 (2.7%) patients in CLEOPATRA phase III trial, 60 (18.4%) patients in a retrospective analysis by Esin et al, and 89 (33.5%) patients in another study including 266 patients (18,19).…”

Section: Discussionmentioning

confidence: 41%

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Treatment Outcomes of HER-2 Positive Metastatic Breast Cancer Patients Treated with Pertuzumab in the First Line Setting- Real Life Experience

Hacioglu¹,

Şahin²

2019

Van Med J

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Objective: Pertuzumab, a new recombinant humanized monoclonal antibody, has been developed to inhibit the formation of HER2:HER3 heterodimerization. The clinical benefit of pertuzumab therapy in HER2 positive metastatic Breast Cancer (mBC) patients in the first-line setting has been shown in previous phase III studies. Herein we aimed to analyze the efficacy and toxicity profile of pertuzumab in patients with HER2 positive mBC. Materials and Methods:This was a retrospective study of 28 patients with mBC followed from two different centers in Turkey. All patients were treated with pertuzumab in the first line setting, with a combination including trastuzumab and docetaxel. Treatment outcomes along with drug efficacy and safety were retrospectively analyzed. Results: At a median follow-up time of 10.1 (2.4-25.2) months, among the 28 patients, 1 (3.6%) case of death and 2 (7.1%) cases of progression occurred. The median age was determined as 47 (18-74) years. Excluding 1 patient, all had (96.4%) de-novo metastatic disease at presentation. The median number of treatment cycles was 7 (4 -12) for docetaxel, 18 (4 -35) for pertuzumab + trastuzumab, and 10 (1 -29) for the maintenance therapy (pertuzumab + trastuzumab). The most common side effects were fatigue (75%) and arthralgia/myalgia (64.3%). Grade 3 or 4 toxicity was observed to be very infrequent as follows: neutropenia; grade 3 in 4 (14%) patients and grade 4 in 1 (3.6%) patient, neuropathy; grade 3 in 5 (17.8%) patients. Conclusion: Even with a small sample size, our results confirm that pertuzumab + trastuzumab + docetaxel combination therapy in the first line setting for HER2 positive mBC patients is the standard of care, with acceptable toxicity profile.Key Words: Metastatic breast cancer, HER2 positive, pertuzumab, progression free survival, overall survival, toxicity ÖZET Amaç: Pertuzumab HER2:HER3 heterodimerizasyon oluşumunu inhibe eden, yeni geliştirilen bir rekombinant humanize monoklonal antikordur. Daha önce yapılan faz III çalışmalarda, HER2 pozitif metastatik Meme Kanseri (mMK) hastalarında pertuzumabın klinik faydası gösterilmiştir. Biz de bu çalışmada HER2 pozitif mMK'li hastalarda pertuzumabın etkinlik ve toksisite profilini analiz etmeyi amaçladık. Gereç ve Yöntemler: Çalışmamızda Türkiye'deki iki farklı merkezden takip edilen 28 mMK hastasının retrospektif verileri incelenmiştir. Tüm hastalar birinci basamakta pertuzumab ile tedavi edilmişti. İlaç etkinliği ve güvenliği ile birlikte tedavi sonuçları retrospektif olarak analiz edildi. Bulgular: Ortanca 10.1 (2.4-25.2) ay takip süresince, toplam 28 hastada, 1 (%3.6) ölüm vakası ve 2 (%7.1) progresyon vakası gerçekleşti. Ortanca yaş 47 (18-74) olarak saptandı. Bir hasta hariç, hastaların hepsi (%96.4) de-novo metastatikti. Ortanca kür sayıları; dosetaksel için 7 (4 -12), pertuzumab + trastuzumab için 18 (4 -35) ve idame pertuzumab + trastuzumab için 10 (1 -29) olarak saptandı. En sık görülen yan etkiler; yorgunluk (%75) ve artralji-myaljiydi (%64.3). Grade 3-4 yan etkiler çok nadir görülmekle birl...

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“…Identification and review of research literature We identified nine eligible studies that included twelve comparisons of trial and non-trial patients: Arrieta et al [28], Bertelli et al [29], De Placido et al [30], Field et al [31], Goldman et al [32], Khera et al [33], Led Du et al [34], Svensson et al [35] and Templeton et al [36]. Figure 2 contains a PRISMA flow diagram showing the selection of studies.…”

Section: Strategies For Dealing With Dilemmasmentioning

confidence: 99%

Are cancer patients better off if they participate in clinical trials? A mixed methods study

et al. 2020

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Background: Research and cancer care are closely intertwined; however, it is not clear whether physicians and nurses believe that clinical trials offer the best treatment for patients and, if so, whether this belief is justified. The aim of this study was therefore: (i) to explore how physicians and nurses perceive the benefits of clinical trial participation compared with standard care and (ii) whether it is justified to claim that clinical trial participation improves outcomes for cancer patients. Methods: A mixed methods approach was used employing semi-structured interviews with 57 physicians and nurses in oncology and haematology and a literature review of the evidence for trial superiority, i.e. the idea that receiving treatment in a clinical trial leads to a better outcome compared with standard care. Inductive thematic analysis was used to examine the interview data. A literature review comprising nine articles was conducted according to a conceptual framework developed by Peppercorn et al. and evaluated recent evidence on trial superiority. Results: Our findings show that many physicians and nurses make claims supporting trial superiority, however very little evidence is available in the literature comparing outcomes for trial participants and non-participants that supports their assertions.

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Human epidermal growth factor receptor 2 dual blockade with trastuzumab and pertuzumab in real life: Italian clinical practice versus the CLEOPATRA trial results

Cited by 32 publications

References 21 publications

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Treatment Outcomes of HER-2 Positive Metastatic Breast Cancer Patients Treated with Pertuzumab in the First Line Setting- Real Life Experience

Are cancer patients better off if they participate in clinical trials? A mixed methods study

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