Xavier Pivot1, Alexey Manikhas2, Bogdan Żurawski2, Ewa Chmielowska2, Boguslawa Karaszewska2, Rozenn Allerton2, Stephen Chan2, Alessandra Fabi2, Paolo Bidoli2, Stefania Gori2, Eva Ciruelos2, Magdolna Dank2, Lajos Hornyak2, Sara Margolin2, Arnd Nusch2, Roma Parikh2, Fareha Nagi2, Michelle DeSilvio2, Sergio Santillana2, Ramona F Swaby2, Vladimir Semiglazov2. 1. Xavier Pivot, Centre Hospitalier Universitaire, Hôpital Jean Minjoz, Besançon, France; Alexey Manikhas, St Petersburg City Oncology Dispensary; Vladimir Semiglazov, Petrov Research Institute of Oncology, St Petersburg, Russian Federation; Bogdan Żurawski, Franciszek Lukaszczyk Oncology Center, Bydgoszcz; Ewa Chmielowska, Centrum Onkologii im. Prof Franciszka Lukaszczyka Oddzial Kliniczny Onkologii, Bydgoszcz, and Uniwersytet Mikolaja Kopernika Torun, Torun; Boguslawa Karaszewska, Przychodnia Lekarska KOMED, ul Wojska Polskiego 6, Konin, Poland; Rozenn Allerton, The Royal Wolverhampton Hospitals National Health Service Trust, Wolverhampton; Stephen Chan, Nottingham University Hospital, Nottingham; Roma Parikh and Fareha Nagi, GlaxoSmithKline, Uxbridge, United Kingdom; Alessandra Fabi, "Regina Elena" National Cancer Institute, Rome; Paolo Bidoli, Azienda Ospedaliera San Gerardo di Monza U.O. Oncologia Medica, Monza, Lombardia; Stefania Gori, Azienda Ospedaliera di Perugia, Ospedale S. Maria della Misericordia, Struttura Complessa di Oncologia Medica, Perugia, Umbria, and Azienda Ospedaliera Sacro Cuore-Don Calabria-Negrar, Negrar, Verona, Italy; Eva Ciruelos, Hospital Universitario 12 de Octubre, Madrid, Spain; Magdolna Dank, SE Radiológiai és Onkoterápiás Klinika; Lajos Hornyak, Veszprém Megyei Csolnoky Ferenc Kórház, Onkológiai Osztály, Budapest, Hungary; Sara Margolin, Karolinska University Hospital, Stockholm, Sweden; Arnd Nusch, Gem Praxis Drs Nusch, Kalhori und Langer, Friedrichstr, Velbert, Germany; and Michelle DeSilvio, Sergio Santillana, and Ramona F. Swaby, GlaxoSmithKline, Collegeville, PA. xavier.pivot@univ-fcomte.fr. 2. Xavier Pivot, Centre Hospitalier Universitaire, Hôpital Jean Minjoz, Besançon, France; Alexey Manikhas, St Petersburg City Oncology Dispensary; Vladimir Semiglazov, Petrov Research Institute of Oncology, St Petersburg, Russian Federation; Bogdan Żurawski, Franciszek Lukaszczyk Oncology Center, Bydgoszcz; Ewa Chmielowska, Centrum Onkologii im. Prof Franciszka Lukaszczyka Oddzial Kliniczny Onkologii, Bydgoszcz, and Uniwersytet Mikolaja Kopernika Torun, Torun; Boguslawa Karaszewska, Przychodnia Lekarska KOMED, ul Wojska Polskiego 6, Konin, Poland; Rozenn Allerton, The Royal Wolverhampton Hospitals National Health Service Trust, Wolverhampton; Stephen Chan, Nottingham University Hospital, Nottingham; Roma Parikh and Fareha Nagi, GlaxoSmithKline, Uxbridge, United Kingdom; Alessandra Fabi, "Regina Elena" National Cancer Institute, Rome; Paolo Bidoli, Azienda Ospedaliera San Gerardo di Monza U.O. Oncologia Medica, Monza, Lombardia; Stefania Gori, Azienda Ospedaliera di Perugia, Ospedale S. Maria della Misericordia, Struttura Complessa di Oncologia Medica, Perugia, Umbria, and Azienda Ospedaliera Sacro Cuore-Don Calabria-Negrar, Negrar, Verona, Italy; Eva Ciruelos, Hospital Universitario 12 de Octubre, Madrid, Spain; Magdolna Dank, SE Radiológiai és Onkoterápiás Klinika; Lajos Hornyak, Veszprém Megyei Csolnoky Ferenc Kórház, Onkológiai Osztály, Budapest, Hungary; Sara Margolin, Karolinska University Hospital, Stockholm, Sweden; Arnd Nusch, Gem Praxis Drs Nusch, Kalhori und Langer, Friedrichstr, Velbert, Germany; and Michelle DeSilvio, Sergio Santillana, and Ramona F. Swaby, GlaxoSmithKline, Collegeville, PA.
Abstract
PURPOSE: CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receivinglapatinib-capecitabine or trastuzumab-capecitabine. PATIENTS AND METHODS: Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: The study was terminated early with 540 enrolled patients (271 receivedlapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. CONCLUSION: CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.
RCT Entities:
PURPOSE: CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with humanepidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. PATIENTS AND METHODS: Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. CONCLUSION: CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.
Authors: Alexandra S Zimmer; Seth M Steinberg; Dee Dee Smart; Mark R Gilbert; Terri S Armstrong; Eric Burton; Nicole Houston; Nadia Biassou; Brunilde Gril; Priscilla K Brastianos; Scott Carter; David Lyden; Stanley Lipkowitz; Patricia S Steeg Journal: Future Oncol Date: 2020-04-09 Impact factor: 3.404
Authors: Marc C Chamberlain; Christina S Baik; Vijayakrishna K Gadi; Shailender Bhatia; Laura Q M Chow Journal: Neuro Oncol Date: 2017-01 Impact factor: 12.300
Authors: Martine Piccart-Gebhart; Eileen Holmes; José Baselga; Evandro de Azambuja; Amylou C Dueck; Giuseppe Viale; Jo Anne Zujewski; Aron Goldhirsch; Alison Armour; Kathleen I Pritchard; Ann E McCullough; Stella Dolci; Eleanor McFadden; Andrew P Holmes; Liu Tonghua; Holger Eidtmann; Phuong Dinh; Serena Di Cosimo; Nadia Harbeck; Sergei Tjulandin; Young-Hyuck Im; Chiun-Sheng Huang; Véronique Diéras; David W Hillman; Antonio C Wolff; Christian Jackisch; Istvan Lang; Michael Untch; Ian Smith; Frances Boyle; Binghe Xu; Henry Gomez; Thomas Suter; Richard D Gelber; Edith A Perez Journal: J Clin Oncol Date: 2015-11-23 Impact factor: 44.544