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Background: Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy. Methods: Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed.

BackgroundLarvae of the tapeworm E. multilocularis cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. A population of stem cell-like cells, the germinative cells, is considered to drive the larval growth and development within the host. The molecular mechanisms controlling the behavior of germinative cells are largely unknown.Methodology/Principal findingsUsing in vitro cultivation systems we show here that the EGFR/ERK signaling in the parasite can promote germinative cell proliferation in response to addition of human EGF, resulting in stimulated growth and development of the metacestode larvae. Inhibition of the signaling by either the EGFR inhibitors CI-1033 and BIBW2992 or the MEK/ERK inhibitor U0126 impairs germinative cell proliferation and larval growth.Conclusions/SignificanceThese data demonstrate the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis.

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<b><i>Introduction:</i></b> In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. <b><i>Methods:</i></b> From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. <b><i>Results:</i></b> At data cutoff of December 16, 2019 (&#x3e;2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7–25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5–30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7–82.2), 59.8% (95% CI 38.8–75.6), and 53.1% (95% CI 31.0–71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5–16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6–47.9) and 33.7% (95% CI 27.3–40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3–22.6) in the TBP group versus 9.4 months (95% CI 5.8–14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3–56.9) versus 33.1% (95% CI 22.3–44.3) and 38.8% (95% CI 29.2–48.4) versus 23.2% (95% CI 13.8–34.1), respectively. No new safety signals of camrelizumab were observed. <b><i>Conclusions:</i></b> With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression.