Efficacy of irinotecan-based chemotherapy after exposure to an anti-PD-1 antibody in patients with advanced esophageal squamous cell carcinoma

Objective:Several anti-programmed cell death 1(anti-PD-1)antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer(ESCC).However,the response to subsequent chemotherapy after the failure of PD-1 blockade in ESCC patients has not been reported,and the optimal sequencing of immunotherapy and chemotherapy remains controversial.The aim of the present study was to evaluate responses to irinotecan-based subsequent chemotherapy in advanced ESCC patients who had progressed after treatment with camrelizumab(SHR-1210),a novel anti-PD-1 antibody.Methods:We retrospectively reviewed the medical records of patients with advanced ESCC treated with camrelizumab at a single institution.Consecutive patients who received subsequent irinotecan-based chemotherapy were selected for data collection and analysis.Results:Overall,a total of 28 patients were included.All patients had received at least two lines of systemic treatment prior to irinotecan salvage.The most common regimen that was administered after PD-1 blockade was irinotecan in combination with 5-fluorouracil(5-Fu)(or its derivatives),which was given to 19 patients.The objective response rate(ORR)and disease control rate(DCR)were 17.9%(5/28)and 64.3%(18/28),respectively,with 5(17.9%)patients achieving a partial response and 13(46.4%)having stable disease.The median progressionfree survival(PFS)was 3.18[95%confidence interval(95%CI),2.48-3.88]months and the median overall survival(OS)was 6.23(95%CI,4.71-7.75)months.No new safety issues,either immune-related or otherwise,were observed.Conclusions:Our results suggested that the response to irinotecan-based chemotherapy after PD-1 blockade in advanced ESCC patients appeared similar to that previously observed in patients who had not received PD-1 antibodies,and further study in larger cohorts or randomized trials is warranted to verify our observation.

Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210

Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events.

Chinese expert consensus on an innovative patient‐centered approach to diagnosis and treatment of cancer

Patient‐centered care(PCC)is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients'experience during the management of their disease.However,despite growing interest,the concept and specifics of PCC remain unclear.This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real‐world practice.These components include daytime diagnostic and treatment procedures,in‐hospital and community‐based infusion centers,home‐based diagnostic and treatment services,smart healthcare solutions,and integration of traditional Chinese medicine.This document delves into the implementation of PCC and explores its potential benefits.

The molecular tumor burden index as a response evaluation criterion in breast cancer

Circulating tumor DNA(ctDNA)is a potential biomarker of prognosis and therapeutic response.We conducted this study to explore the role of the molecular tumor burden index(mTBI)in ctDNA as a therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study.We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study(NCT01917279).Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples.The pretreatment mTBI value was correlated with tumor burden(P=0.025).Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI,and the median overall survival was 40.9 months and 68.4 months,respectively(P=0.011).Patients with mTBI decrease to less than 0.02%at the first tumor evaluation had longer progression-free survival and overall survival(P<0.001 and P=0.007,respectively).The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans(88.5%and 87.5%,respectively).The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort(P<0.001 and P=0.036,respectively),as well as in the cohort in which computed tomography scans were defined as representing stable disease(P=0.027 and P=0.015,respectively).The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.

Recombinant human thrombopoietin prior to mobilization chemotherapy facilitates platelet recovery in autologous transplantation in patients with lymphoma:Results of a prospective randomized study

Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukapheresis.This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods:In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm).The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results:Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs.1 unit,P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 ×10^(9)/L (range 18-219) among patients who received rhTPO and 73 ×10^(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 ×10^(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%,P=0.297).Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 ×10^(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4],P=0.011).The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 andP=0.067,respectively).Conclusions:Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells,but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration:This trial has been registered in Clinicaltrials.gov as NCT03014102.

Progress in systemic therapy for triple-negative breast cancer

Triple-negative breast cancer(TNBC)is the most aggressive subtype of breast cancer with a heterogeneous genetic profile.Chemotherapy exhibits substantial activity in a small subset of these patients.Drug resistance is inevitable.Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention.Such progress has translated into major advances in treatment strategies,including modified chemotherapy approaches,immune checkpoint inhibitors,and targeted therapeutic drugs.All of these strategies have been evaluated in clinical trials.Nevertheless,patient selection remains a considerable challenge in clinical practice.

Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies:real-world data in the Han population

Background:This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive(ER+)metastatic breast cancer in routine clinical practice.Methods:The clinical data of patients with ER+metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database.The efficacy profile of palbociclib in this Han population was evaluated,especially for various combination regimens.The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.Results:A total of 186 patients from 89 cities in 18 provinces in China were enrolled.The median progression-free survival(PFS)was similar among different palbociclib-combined groups(P=0.566):10.0 months(95%confidence interval[CI]3.8-16.1)in the+exemestane group,9.7 months(95%CI 6.3-13.1)in the+letrozole group,7.8 months(95%CI 5.5-10.2)in the+fulvestrant group,7.2 months(95%CI 3.2-11.3)in the+toremifene group,and 6.1 months(95%CI 1.2-11.0)in the+anastrozole group.Thirty-four patients(18.3%)had received everolimus for their metastatic disease before the prescription of palbociclib.The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group(50.0%vs.82.2%,P<0.001).Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group(3.4 months vs.8.8 months,P=0.001).After propensity score matching,patients pre-treated with everolimus had similar PFS(4.4 months,95%CI 0.5-8.2)compared with everolimus-naïve patients(6.1 months,95%CI 4.7-7.5,P=0.439).Conclusions:Various palbociclib-based regimens have promising efficacy in ER+metastatic breast cancer in real-world settings,even in patients who had been pre-treated with everolimus.