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.
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Data sharing
The dataset used during the present study are available from the corresponding author upon reasonable request.
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All patients alive at the time of data collection provided informed consent to participate to this retrospective observational non-interventional study. The procedures followed were in accordance with the precepts of Good Clinical Practice and the declaration of Helsinki. The study was approved by the respective local ethical committees on human experimentation of each institution, after previous approval by the coordinating center (Comitato Etico delle Province di L’Aquila e Teramo, protocol number 21, approved on July 16, 2020).
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All patients alive at the time of data collection provided an informed consent to participate to this retrospective observational non-interventional study.
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A.P. reported receiving advisory board fees from GSK. A.C. reported receiving consulting/advisory board fees from Astrazeneca, MSD, Roche and BMS; speakers’ fee from Novartis, Astellas, MSD, Astrazeneca. A.P. reported receiving fees from Eli-Lilly, MSD and Servier. R.G. reported receiving fees from Amgen and Servier and advisory board fees from Amgen, Servier, Bayer and Merck-Serono. GS reported receiving advisory board/Editorial fees from: Novartis, Servier, Teva, Bayer, Genetic, Epionpharma.
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Antonetti, P., Fargnoli, M.C., Porzio, G. et al. A multicenter study of skin toxicity management in patients with left-sided, RAS/BRAF wild-type metastatic colorectal cancer treated with first-line anti-EGFR-based doublet regimen: is there room for improvement?. Support Care Cancer 30, 2455–2465 (2022). https://doi.org/10.1007/s00520-021-06652-5
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DOI: https://doi.org/10.1007/s00520-021-06652-5