Marta Polkowska1,2, Paweł Ekk-Cierniakowski3,4, Edyta Czepielewska5, Wojciech Wysoczański3, Wojciech Matusewicz3, Małgorzata Kozłowska-Wojciechowska5. 1. Department of Clinical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Medical University of Warsaw, Banacha St. 1, 02-097, Warsaw, Poland. marta.polkowska@wum.edu.pl. 2. Agency for Health Technology Assessment and Tariff Systems, Warsaw, Poland. marta.polkowska@wum.edu.pl. 3. Agency for Health Technology Assessment and Tariff Systems, Warsaw, Poland. 4. Collegium of Economic Analysis, Warsaw School of Economics, Warsaw, Poland. 5. Department of Clinical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Medical University of Warsaw, Banacha St. 1, 02-097, Warsaw, Poland.
Abstract
PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH). The main objective was to assess the overall survival of melanoma patients treated in real-world conditions, taking into account sequences of treatment. RESULTS: We identified 3397 patients with malignant melanoma treated for the first line and the second line. Patients receiving CTH were significantly older than those treated with the novel drugs. At the same time, the population treated with immunotherapy and targeted therapy was well balanced. Overall survival was significantly better for the novel drugs compared to classic chemotherapy in both lines (for the first line, VEM vs CTH HR = 0.72, 95% CI 0.65-0.81; p < .01, and for the second line, VEM vs CTH HR = 0.78, 95% CI 0.62-0.98; p = .03; IPI vs CTH HR = 0.72, 95% CI 0.62-0.86; p < .01). There was no statistically significant difference for IPI vs VEM; however, subgroup analysis revealed superior results in the case of the CTH-IPI over BRAFi-IPI sequence. CONCLUSION: Novel drugs for melanoma provide a significant advantage in survival over classic chemotherapy. Comparative assessment of IPI and VEM indicated no difference, but only immunotherapy-treated patients achieved long-lasting results. Our data on sequential treatment indicate that immunotherapy might be a better option for the first line rather than targeted therapy, but that conclusion requires further studies of the best way to manage the treatment of melanoma patients.
PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH). The main objective was to assess the overall survival of melanomapatients treated in real-world conditions, taking into account sequences of treatment. RESULTS: We identified 3397 patients with malignant melanoma treated for the first line and the second line. Patients receiving CTH were significantly older than those treated with the novel drugs. At the same time, the population treated with immunotherapy and targeted therapy was well balanced. Overall survival was significantly better for the novel drugs compared to classic chemotherapy in both lines (for the first line, VEM vs CTH HR = 0.72, 95% CI 0.65-0.81; p < .01, and for the second line, VEM vs CTH HR = 0.78, 95% CI 0.62-0.98; p = .03; IPI vs CTH HR = 0.72, 95% CI 0.62-0.86; p < .01). There was no statistically significant difference for IPI vs VEM; however, subgroup analysis revealed superior results in the case of the CTH-IPI over BRAFi-IPI sequence. CONCLUSION: Novel drugs for melanoma provide a significant advantage in survival over classic chemotherapy. Comparative assessment of IPI and VEM indicated no difference, but only immunotherapy-treated patients achieved long-lasting results. Our data on sequential treatment indicate that immunotherapy might be a better option for the first line rather than targeted therapy, but that conclusion requires further studies of the best way to manage the treatment of melanomapatients.
Authors: F Stephen Hodi; Steven J O'Day; David F McDermott; Robert W Weber; Jeffrey A Sosman; John B Haanen; Rene Gonzalez; Caroline Robert; Dirk Schadendorf; Jessica C Hassel; Wallace Akerley; Alfons J M van den Eertwegh; Jose Lutzky; Paul Lorigan; Julia M Vaubel; Gerald P Linette; David Hogg; Christian H Ottensmeier; Celeste Lebbé; Christian Peschel; Ian Quirt; Joseph I Clark; Jedd D Wolchok; Jeffrey S Weber; Jason Tian; Michael J Yellin; Geoffrey M Nichol; Axel Hoos; Walter J Urba Journal: N Engl J Med Date: 2010-06-05 Impact factor: 91.245
Authors: Allison Ackerman; Oliver Klein; David F McDermott; Wei Wang; Nageatte Ibrahim; Donald P Lawrence; Anasuya Gunturi; Keith T Flaherty; F Stephen Hodi; Richard Kefford; Alexander M Menzies; Michael B Atkins; Georgina V Long; Ryan J Sullivan Journal: Cancer Date: 2014-02-27 Impact factor: 6.860
Authors: Andrea Forschner; Felizitas Eichner; Teresa Amaral; Ulrike Keim; Claus Garbe; Thomas Kurt Eigentler Journal: J Cancer Res Clin Oncol Date: 2016-11-22 Impact factor: 4.553
Authors: Charles M Balch; Seng-jaw Soong; Jeffrey E Gershenwald; John F Thompson; Daniel G Coit; Michael B Atkins; Shouluan Ding; Alistair J Cochran; Alexander M M Eggermont; Keith T Flaherty; Phyllis A Gimotty; Timothy M Johnson; John M Kirkwood; Stanley P Leong; Kelly M McMasters; Martin C Mihm; Donald L Morton; Merrick I Ross; Vernon K Sondak Journal: Ann Surg Oncol Date: 2013-07-10 Impact factor: 5.344
Authors: James Larkin; Michele Del Vecchio; Paolo A Ascierto; Ivana Krajsova; Jacob Schachter; Bart Neyns; Enrique Espinosa; Claus Garbe; Vanna Chiarion Sileni; Helen Gogas; Wilson H Miller; Mario Mandalà; Geke A P Hospers; Ana Arance; Paola Queirolo; Axel Hauschild; Michael P Brown; Lada Mitchell; Luisa Veronese; Christian U Blank Journal: Lancet Oncol Date: 2014-02-27 Impact factor: 41.316
Authors: F Aya; A Fernandez-Martinez; L Gaba; I Victoria; M Tosca; E Pineda; P Gascon; A Prat; A Arance Journal: Clin Transl Oncol Date: 2016-05-04 Impact factor: 3.405
Authors: Thomas K Eigentler; Max Schlaak; Jessica C Hassel; Carmen Loquai; Ingo Stoffels; Ralf Gutzmer; Sylvie Pätzold; Peter Mohr; Ulrich Keller; Hans Starz; Jens Ulrich; Athanasios Tsianakas; Katharina Kähler; Axel Hauschild; Eva Janssen; Beatrice Schuler-Thurner; Benjamin Weide; Claus Garbe Journal: J Immunother Date: 2014-09 Impact factor: 4.456
Authors: Vanna Chiarion Sileni; Jacopo Pigozzo; Paolo Antonio Ascierto; Antonio Maria Grimaldi; Michele Maio; Lorenza Di Guardo; Paolo Marchetti; Francesco de Rosa; Carmen Nuzzo; Alessandro Testori; Emilia Cocorocchio; Maria Grazia Bernengo; Michele Guida; Riccardo Marconcini; Barbara Merelli; Giorgio Parmiani; Gaetana Rinaldi; Massimo Aglietta; Marco Grosso; Paola Queirolo Journal: J Exp Clin Cancer Res Date: 2014-04-04
Authors: I Márquez-Rodas; A Arance; A Berrocal; C L Larios; J Curto-García; I X Campos-Tapias; A B Blanca; S Martin-Algarra Journal: Clin Transl Oncol Date: 2019-08-21 Impact factor: 3.405
Authors: Paolo A Ascierto; Antoni Ribas; James Larkin; Grant A McArthur; Karl D Lewis; Axel Hauschild; Keith T Flaherty; Edward McKenna; Qian Zhu; Yong Mun; Brigitte Dréno Journal: J Transl Med Date: 2020-08-03 Impact factor: 5.531
Authors: Wei Fang Dai; Jaclyn M Beca; Ruth Croxford; Wanrudee Isaranawatchai; Ines B Menjak; Teresa M Petrella; Nicole Mittmann; Craig C Earle; Scott Gavura; Timothy P Hanna; Kelvin K W Chan Journal: BMC Cancer Date: 2020-04-15 Impact factor: 4.430