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.

Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study / A. Raimondi, S. Corallo, S. Lonardi, C. Antoniotti, L. Rimassa, A. Amatu, M. Tampellini, P. Racca, R. Murialdo, M. Clavarezza, A. Zaniboni, G. Toscano, G. Tomasello, F. Petrelli, L. Antonuzzo, M. Giordano, S. Cinieri, R. Longarini, M. Niger, M. Antista, M. Ambrosini, F. Pagani, M. Prisciandaro, G. Randon, F. de Braud, M. Di Bartolomeo, F. Pietrantonio, F. Morano. - In: SUPPORTIVE CARE IN CANCER. - ISSN 0941-4355. - 29:7(2021 Jul), pp. 3971-3980. [10.1007/s00520-020-05972-2]

Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study

G. Toscano;G. Tomasello;F. Petrelli;M. Prisciandaro;G. Randon;F. de Braud;M. Di Bartolomeo;F. Pietrantonio
Penultimo
;
2021-07

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.
Adverse events; Colorectal cancer; EGFR inhibitor; Metastasis; Skin rash; Tetracyclines; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Doxycycline; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Panitumumab; Skin Diseases
Settore MED/06 - Oncologia Medica
gen-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/908250
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