Hedgehog Inhibitors Beyond Clinical Complete Response in Basal Cell Carcinoma: Should I Stop or Should I Go?

Autor:	Alfieri, Salvatore, Romanò, Rebecca, Marceglia, Sara, Giorgi, Vincenzo De, Peris, Ketty, Sollena, Pietro, Piccerillo, Alfredo, Moro, Ruggero, Gualdi, Giulio, Ascierto, Paolo Antonio, Palla, Marco, Paone, Miriam, Eibenschutz, Laura, Spagnolo, Francesco, Queirolo, Paola, Filippini, Daria Maria, Cavalieri, Stefano, Resteghini, Carlo, Bergamini, Cristiana, Manocchio, Antonello
Předmět:	STATISTICAL correlation PEARSON correlation (Statistics) DRUG toxicity HEDGEHOG signaling proteins CANCER relapse RESEARCH funding PATHOLOGIC complete response TERMINATION of treatment DISEASE remission TREATMENT effectiveness CANCER patients RETROSPECTIVE studies TREATMENT duration DESCRIPTIVE statistics AMIDES RESEARCH PYRIDINE BASAL cell carcinoma COMPARATIVE studies PROGRESSION-free survival CHEMICAL inhibitors
Zdroj:	Oncologist; May2024, Vol. 29 Issue 5, pe699-e707, 9p
Abstrakt:	Introduction In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need. Materials and Methods We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson's correlation coefficient (P  < .05) and Bayesian statistics (BF10). Results Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N  = 43, 63%), without Gorlin syndrome (N  = 56, 82%) and with head and neck area as primary site (N  = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N  = 50/61) due to toxicity (R1), and 18% (N  = 11/61) due to recurrence (R2). Conversely, 10% (N  = 7/68) continued vismodegib until last follow-up. In the whole population (N  = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P  < .01, BF10 = 39.2) and TTD (P  < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N  = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N  = 38, r  = 0.44, P  < .01) and in the recurrent patients who stopped vismodegib for toxicity (N  = 26, r  = 0.665, P  < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N  = 54 vs. ≤ 2 months, N  = 14: 470 vs. 175 d, P  < .01). Conclusions Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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