Risultati per: Carcinoma cutaneo a cellule squamose

To the Editor Qin and colleagues conducted an important trial to compare tislelizumab with sorafenib. The study was designed within a noninferiority setting for overall survival (OS) by claiming tislelizumab would be noninferior to sorafenib if the upper bound of the 95.003% CI for the hazard ratio (HR) was less than 1.08. The observed HR was 0.85 with a 95.003% CI of 0.71 to 1.02. The objective response rates were 14.3% and 5.4% for tislelizumab and sorafenib, respectively. The corresponding median durations of response were 36.1 and 11.0 months, respectively. There are several issues that may deserve our attention for conducting future clinical studies in a similar setting.

In Reply We appreciate the interest in our article by Faries and Venna et al as well as their comments on the analysis. While we agree that there are inherent limitations to retrospective studies of survival outcomes using registry data, we believe that it is prudent to glean what insights we can from these datasets given the lack of large-scale studies of rare cancers, such as Merkel cell carcinoma (MCC), in the existing literature.

In Reply I thank and have provided responses to Sun et al for their comments on our article that compared tislelizumab vs sorafenib in first-line treatment of unresectable hepatocellular carcinoma. The noninferiority margin of 1.08 is clearly clinically justifiable. It is based on the data from the 2 sorafenib trials in first-line hepatocellular carcinoma (HCC), namely the SHARP trial. Using the 95% CI lower limit method on log hazard ratio (HR) as described in Rothmann et al, the noninferiority margin corresponding to 60% retention of the sorafenib effect vs placebo was calculated as 1.08. Given the consistent survival improvement of sorafenib vs placebo demonstrated in the SHARP and Asia-Pacific trials, and the fact that, at the time the BGB-A317-301 study was designed, no other monotherapy treatment was able to show superiority compared with sorafenib since its approval in 2007, a margin of 1.08 derived from 2 well-conducted phase 3 pivotal trials was statistically persuasive. Notably, the same margin was used in other noninferiority monotherapy HCC trials, namely the REFLECT (lenvatinib) and HIMALAYA (durvalumab) trials.

To the Editor I read with interest the recent article by Cheraghlou and colleagues regarding primary tumor excision techniques in Merkel cell carcinoma (MCC). The article’s central observation, an association between the use of Mohs surgery and improved overall survival (OS) compared with wide excision, appears to be accurate. However, the assertion that Mohs surgery provides a “more effective treatment for MCC primary tumors than conventional” wide local excision does not appear to be supported by the presented data.

To the Editor We read with interest the analysis comparing unadjusted overall survival (OS) of Mohs micrographic surgery (MMS) vs excision using the National Cancer Database (NCDB) for stage 1 and 2 Merkel cell carcinoma (MCC). MMS was associated with improved OS vs wide local excision (WLE) with an approximately 40% reduction in deaths. However, we cannot endorse the authors’ conclusion that MMS “may provide a more effective treatment for MCC” as it is inconsistent with what is known about MCC. A systematic review of 31 studies (retrospective and case series) comparing WLE and MMS for MCC did not show a difference in outcomes. A recent NCDB analysis of early-stage MCC during an overlapping period (2004-2014 vs 2004-2018 as in the current study) failed to detect a survival advantage with MMS. The present study was larger than the prior NCDB analysis and required pathologic nodal staging. Of the 2312 patients analyzed, 4.5% underwent MMS vs 95.5% who underwent a form of excision (narrow margin excision or WLE). Compared with the MMS group, the WLE group had an approximately 2-fold higher incidence of lymphovascular invasion (13.9% vs 7.7%), a comorbidity index of 2 or higher (4.6% vs 1.9%), and pT2 MCC (20.8% vs 11.5%). Although a multivariable regression model considering these covariates found improved OS with MMS, it is likely that the unidentified confounding variables were associated with the difference. Patients with stage 1 and 2 MCC have high disease-specific survival, with most MCC-specific deaths occurring within 3 years and many deaths due to intercurrent disease. In the present study, the OS differences were not detected until 3 years or later, suggesting other-cause mortality for the difference. The study also examined adjuvant radiotherapy (RT) use. National Comprehensive Cancer Network guidelines recommend that most patients with MCC be considered for adjuvant RT. Seventy percent of patients in the MMS group had MCC of the head and neck (H/N). However, RT was recorded for only 45%. The H/N location is considered a high-risk feature for MCC recurrence and death, and a recent study found that adjuvant RT for stage 1 H/N MCC may be associated with decreased recurrence rates. We are concerned that RT is being underused or underreported. The authors of the present study acknowledged several limitations of using the NCDB, including the lack of disease-specific survival data and the small MMS cohort. We advise caution when interpreting the results, mostly because observed survival differences may not reflect MCC-specific deaths.