Pembrolizumab versus Ipilimumab in Advanced Melanoma
Caroline Robert, Jacob Schachter, Georgina V Long, Ana Arance, Jean Jacques Grob, Laurent Mortier, Adil Daud, Matteo S Carlino, Catriona McNeil, Michal Lotem, James Larkin, Paul Lorigan, Bart Neyns, Christian U Blank, Omid Hamid, Christine Mateus, Ronnie Shapira-Frommer, Michele Kosh, Honghong Zhou, Nageatte Ibrahim, Scot Ebbinghaus, Antoni Ribas, KEYNOTE-006 investigators, Matteo S Carlino, Jonathan Cebon, Peter Hersey, Georgina Long, Catriona McNeil, Michael Millward, Euan Walpole, Christoph Höller, Helmut Kehrer, Erika Richtig, Matthias Schmuth, Jean-François Baurain, Bart Neyns, Pascal Wolter, Marcus Butler, Elaine McWhirter, Wilson Miller, Teresa Petrella, Alejandro Acevedo, Christian Caglevic, Luisa Morales, Jesús Sanchez, Andres Yepes, Angela Regina Zambrano, Marie-Francoise Avril, Caroline Dutriaux, Jean Jacques Grob, Bernard Guilot, Jean-Phillippe Lacour, Marie-Therese Leccia, Delphine Legoupil, Celeste Lebbe, Laurent Machet, Laurent Mortier, Caroline Robert, Carola Berking, Carmen Loquai, Peter Mohr, Dirk Schadendorf, Jochen Utikal, Gil Bar-Sela, Michal Lotem, Jacob Schachter, Christian Blank, Catherine Barrow, Bernie Fitzharris, Christian Kersten, Marta Nyakas, Oddbjørn Straume, Ana Arance, Alfonso Berrocal, Javier Cortes, Enrique Espinosa, Jose Lopez-Martin, Salvador Martin-Algarra, Giuseppe Masucci, Karin Papworth, Gustav Ullenhag, Ewan Brown, David Chao, Thomas Evans, James Larkin, Paul Lorigan, Mark Middleton, Sunil Skaria, Neil Steven, Sanjiv Agarwala, Shailender Bhatia, Adil Daud, Tara Gangadhar, Rene Gonzalez, Omid Hamid, Pallavi Kumar, Timothy Kuzel, Jose Lutzky, Steven O'Day, David Perry, Andrew Pecora, Igor Puzanov, Antoni Ribas, Karen Slezak, Mario Sznol, Ahmad Tarhini, Geoffrey Weiss, Caroline Robert, Jacob Schachter, Georgina V Long, Ana Arance, Jean Jacques Grob, Laurent Mortier, Adil Daud, Matteo S Carlino, Catriona McNeil, Michal Lotem, James Larkin, Paul Lorigan, Bart Neyns, Christian U Blank, Omid Hamid, Christine Mateus, Ronnie Shapira-Frommer, Michele Kosh, Honghong Zhou, Nageatte Ibrahim, Scot Ebbinghaus, Antoni Ribas, KEYNOTE-006 investigators, Matteo S Carlino, Jonathan Cebon, Peter Hersey, Georgina Long, Catriona McNeil, Michael Millward, Euan Walpole, Christoph Höller, Helmut Kehrer, Erika Richtig, Matthias Schmuth, Jean-François Baurain, Bart Neyns, Pascal Wolter, Marcus Butler, Elaine McWhirter, Wilson Miller, Teresa Petrella, Alejandro Acevedo, Christian Caglevic, Luisa Morales, Jesús Sanchez, Andres Yepes, Angela Regina Zambrano, Marie-Francoise Avril, Caroline Dutriaux, Jean Jacques Grob, Bernard Guilot, Jean-Phillippe Lacour, Marie-Therese Leccia, Delphine Legoupil, Celeste Lebbe, Laurent Machet, Laurent Mortier, Caroline Robert, Carola Berking, Carmen Loquai, Peter Mohr, Dirk Schadendorf, Jochen Utikal, Gil Bar-Sela, Michal Lotem, Jacob Schachter, Christian Blank, Catherine Barrow, Bernie Fitzharris, Christian Kersten, Marta Nyakas, Oddbjørn Straume, Ana Arance, Alfonso Berrocal, Javier Cortes, Enrique Espinosa, Jose Lopez-Martin, Salvador Martin-Algarra, Giuseppe Masucci, Karin Papworth, Gustav Ullenhag, Ewan Brown, David Chao, Thomas Evans, James Larkin, Paul Lorigan, Mark Middleton, Sunil Skaria, Neil Steven, Sanjiv Agarwala, Shailender Bhatia, Adil Daud, Tara Gangadhar, Rene Gonzalez, Omid Hamid, Pallavi Kumar, Timothy Kuzel, Jose Lutzky, Steven O'Day, David Perry, Andrew Pecora, Igor Puzanov, Antoni Ribas, Karen Slezak, Mario Sznol, Ahmad Tarhini, Geoffrey Weiss
Abstract
Background: The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma.
Methods: In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progression-free and overall survival.
Results: The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P=0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P=0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%).
Conclusions: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials.gov number, NCT01866319.).
Source: PubMed