Paolo Antonetti1,2, Maria Concetta Fargnoli3,4, Giampiero Porzio2,5, Lisa Salvatore6,7, Roberto Filippi8,9,10, Michele Ghidini11, Olga Nigro12, Fabio Gelsomino13, Ina Valeria Zurlo14, Emanuela Dell'Aquila15, Pasquale Lombardi16, Susana Roselló Keränen17, Ilaria Depetris18, Riccardo Giampieri19, Cristina Morelli20, Michele De Tursi21,22, Francesca Romana Di Pietro23, Nicoletta Zanaletti24, Pasquale Vitale25,26, Ingrid Garajova27, Gian Paolo Spinelli28, Federica Zoratto29, Michela Roberto30, Angelica Petrillo31, Giacomo Aimar6,7, Alessio Cortellini2,32, Maria Vittoria Pensieri2,5, Corrado Ficorella2,5, Claudio Ferri33, Alessandro Parisi5,33. 1. Dermatology, St. Salvatore Hospital, L'Aquila, Italy. 2. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy. 3. Dermatology, St. Salvatore Hospital, L'Aquila, Italy. fargnoli@univaq.it. 4. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy. fargnoli@univaq.it. 5. Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy. 6. Università Cattolica del Sacro Cuore, Rome, Italy. 7. Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy. 8. Department of Oncology, University of Turin, Torino, Italy. 9. Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy. 10. Centro Oncologico Ematologico Subalpino, Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy. 11. Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. 12. Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy. 13. Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy. 14. Medical Oncology, "Vito Fazzi" Hospital, Lecce, Italy. 15. Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome, Italy. 16. Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain. 17. CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. 18. Medical Oncology, ASL TO4, Ospedale Civile di Ivrea, Ivrea, Turin, Italy. 19. Clinica Oncologica e Centro Regionale di Genetica Oncologica, Università Politecnica delle Marche, AOU Ospedali Riuniti, Ancona, Italy. 20. Medical Oncology Unit and PhD program in Systems and Experimental Medicine (XXXV cycle), Tor Vergata University Hospital, Viale Oxford, 81, 00133, Rome, Italy. 21. Department of Medical, Oral and Biotechnological Sciences and Center for Advance Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy. 22. Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy. 23. IRCCS Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy. 24. Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G.Pascale, Napoli, Italy. 25. Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131, Napoli, Italy. 26. Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy. 27. Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126, Parma, Italy. 28. UOC Territorial Oncology - AUSL Latina-CdS Aprilia - University of Rome "Sapienza", Latina, Italy. 29. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 30. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant'Andrea Hospital, Rome, Italy. 31. Medical Oncology Unit, Ospedale del Mare, Naples, Italy. 32. Department of Surgery and Cancer, Imperial College London, London, UK. 33. Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Abstract
BACKGROUND: Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines have only recently been published. AIM AND METHODS: To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%, p < 0.001) and in patients treated with panitumumab (76.1% vs 93.7%, p < 0.001) or cetuximab (83.3% vs 95.4%, p = 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%, p = 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%, p = 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively, p = 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively, p < 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months). CONCLUSION: Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients' quality of life without compromising the continuity and efficacy of antineoplastic therapy.
BACKGROUND: Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines have only recently been published. AIM AND METHODS: To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%, p < 0.001) and in patients treated with panitumumab (76.1% vs 93.7%, p < 0.001) or cetuximab (83.3% vs 95.4%, p = 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%, p = 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%, p = 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively, p = 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively, p < 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months). CONCLUSION: Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients' quality of life without compromising the continuity and efficacy of antineoplastic therapy.
Authors: E Van Cutsem; A Cervantes; R Adam; A Sobrero; J H Van Krieken; D Aderka; E Aranda Aguilar; A Bardelli; A Benson; G Bodoky; F Ciardiello; A D'Hoore; E Diaz-Rubio; J-Y Douillard; M Ducreux; A Falcone; A Grothey; T Gruenberger; K Haustermans; V Heinemann; P Hoff; C-H Köhne; R Labianca; P Laurent-Puig; B Ma; T Maughan; K Muro; N Normanno; P Österlund; W J G Oyen; D Papamichael; G Pentheroudakis; P Pfeiffer; T J Price; C Punt; J Ricke; A Roth; R Salazar; W Scheithauer; H J Schmoll; J Tabernero; J Taïeb; S Tejpar; H Wasan; T Yoshino; A Zaanan; D Arnold Journal: Ann Oncol Date: 2016-07-05 Impact factor: 32.976
Authors: Michele De Tursi; Marinella Zilli; Consiglia Carella; Matteo Auriemma; Maria Nadia Lisco; Marta Di Nicola; Giuseppe Di Martino; Clara Natoli; Paolo Amerio Journal: Onco Targets Ther Date: 2017-06-16 Impact factor: 4.147