Alessandra Raimondi1, Salvatore Corallo1, Sara Lonardi2, Carlotta Antoniotti3, Lorenza Rimassa4,5, Alessio Amatu6, Marco Tampellini7, Patrizia Racca8, Roberto Murialdo9, Matteo Clavarezza10, Alberto Zaniboni11, Giuseppe Toscano12, Gianluca Tomasello13, Fausto Petrelli14, Lorenzo Antonuzzo15,16, Monica Giordano17, Saverio Cinieri18, Raffaella Longarini19, Monica Niger1, Maria Antista1, Margherita Ambrosini1, Filippo Pagani1, Michele Prisciandaro1,20, Giovanni Randon1, Filippo de Braud1,20, Maria Di Bartolomeo1, Filippo Pietrantonio21,22, Federica Morano1. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy. 2. Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto-IRCCS, Padua, Italy. 3. Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy. 4. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy. 5. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. 6. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. 7. Department of Oncology, AOU San Luigi di Orbassano, University of Torino, Orbassano, Italy. 8. Colorectal Cancer Unit, Medical Oncology Division 1, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy. 9. Department of Internal Medicine, University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy. 10. Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy. 11. Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. 12. Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy. 13. Medical Oncology Unit, ASST Ospedale di Cremona, Cremona, Italy. 14. Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio, Italy. 15. Clinical Oncology Unit, AOU Careggi, Florence, Italy. 16. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 17. Medical Oncology Unit, Azienda Socio Sanitaria Territoriale Lariana, Como, Italy. 18. Medical Oncology Unit, Ospedale Antonio Perrino, Brindisi, Italy. 19. Medical Oncology Unit, Azienda Ospedaliera San Gerardo, Monza, Italy. 20. Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. 21. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy. filippo.pietrantonio@istitutotumori.mi.it. 22. Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. filippo.pietrantonio@istitutotumori.mi.it.
Abstract
INTRODUCTION: The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available. METHODS: We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity. We assessed the rate of treatment-related and panitumumab-related adverse events (AEs), treatment intensity, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 226 patients, out of the 229 enrolled in the Valentino study, were eligible for the analysis. Overall, 143 (63%) and 83 (37%) patients received or not the antibiotic prophylaxis for skin toxicity. Any grade and G3/4 panitumumab-related AEs were reported in 89% versus 92% (p = 0.650) and 27% versus 27% (p = 1.000) patients who received or not the pre-emptive prophylaxis, respectively. Any grade and G3/4 skin rash occurred in 81% versus 90% (p = 0.085) and 27% versus 25% (p = 0.876) patients receiving or not the prophylaxis, respectively. No significant differences in terms of treatment duration, treatment delays or dose reductions, PFS, and OS were observed in the two sub-populations. CONCLUSION: The adequate management of anti-EGFR-related skin toxicity is fundamental to optimize the outcome of mCRC patients, balancing the survival benefit with patients' quality of life, especially in the first-line setting.
RCT Entities:
INTRODUCTION: The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available. METHODS: We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity. We assessed the rate of treatment-related and panitumumab-related adverse events (AEs), treatment intensity, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 226 patients, out of the 229 enrolled in the Valentino study, were eligible for the analysis. Overall, 143 (63%) and 83 (37%) patients received or not the antibiotic prophylaxis for skin toxicity. Any grade and G3/4 panitumumab-related AEs were reported in 89% versus 92% (p = 0.650) and 27% versus 27% (p = 1.000) patients who received or not the pre-emptive prophylaxis, respectively. Any grade and G3/4 skin rash occurred in 81% versus 90% (p = 0.085) and 27% versus 25% (p = 0.876) patients receiving or not the prophylaxis, respectively. No significant differences in terms of treatment duration, treatment delays or dose reductions, PFS, and OS were observed in the two sub-populations. CONCLUSION: The adequate management of anti-EGFR-related skin toxicity is fundamental to optimize the outcome of mCRC patients, balancing the survival benefit with patients' quality of life, especially in the first-line setting.