Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma

Abstract Background There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). Methods Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. Results No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’s ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. Conclusions The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

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Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Cancers ◽

10.3390/cancers12010036 ◽

2019 ◽

Vol 12 (1) ◽

pp. 36 ◽

Cited By ~ 5

Author(s):

Antonio Facciorusso ◽

Mohamed A. Abd El Aziz ◽

Rodolfo Sacco

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Adverse Events ◽

Therapeutic Option ◽

Controlled Trial ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Sensitivity Analyses ◽

Free Survival

Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46–12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68–3.86). The pooled objective response rate was 10.1% (7.8–12.5%) while the disease control rate was 65.5% (61.3–69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

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Transarterial Chemoembolization Combined with Iodine 125 Seeds Versus Transarterial Chemoembolization Combined with Radiofrequency Ablation in the Treatment of Early- and Intermediate-stage Hepatocellular Carcinoma

10.21203/rs.2.21964/v2 ◽

2020 ◽

Author(s):

chen lei ◽

Xuefeng Kan ◽

Tao Sun ◽

Yanqiao Ren ◽

Yanyan Cao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Transarterial Chemoembolization ◽

Combined Treatment ◽

Objective Response ◽

Progression Free Survival ◽

Intermediate Stage ◽

Treatment Groups ◽

Pugh Class ◽

Iodine 125

Abstract Background:Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are options treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC. Methods: The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups.Results: In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41 months vs. 36 months; PFS: 18 months vs. 15 months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P > 0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P = 0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P = 0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented.Conclusions: The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.

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Evaluation of doxorubicin-eluting bead transcatheter arterial chemoembolization combined with endovascular brachytherapy for hepatocellular carcinoma with main portal vein tumor thrombus

10.21203/rs.3.rs-52846/v2 ◽

2020 ◽

Author(s):

Zhiyuan Wu ◽

Ju Gong ◽

Wei Huang ◽

Qingbing Wang ◽

Ziyin Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Portal Vein ◽

Tumor Thrombus ◽

Transcatheter Arterial Chemoembolization ◽

Main Portal Vein ◽

Tace Group ◽

Iodine 125 ◽

Arterial Chemoembolization

Abstract Background The goal of this study was to compare the clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular stent implantation with an iodine-125 seed strand in hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT).Methods This study was a prospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were randomly divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. The time to disease progression and survival rate were compared between the two groups.Results A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3±98.2 days in the C-TACE group and 101.7±90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times.Conclusion Endovascular implantation of a stent with an iodine-125 seed strand combined with TACE is safe and effective in HCC patients with MPVTT. Compared to C-TACE, D-TACE achieves more benefits regarding PFS and OS.Trial registration This study was a cohort study, no health-related interventions to evaluate the effects on health outcomes. This study wasn’t a clinical trial.

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Hepatocellular carcinoma with tumor thrombus in portal vein branch: Transarterial chemoembolization combined with Iodine125 brachytherapy versus transarterial chemoembolization combined with sorafenib.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15646 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15646-e15646

Author(s):

Jingjun Huang ◽

Wensou Huang ◽

Mingyue Cai ◽

Yongjian Guo ◽

Jingwen Zhou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Portal Vein ◽

Transarterial Chemoembolization ◽

Tumor Thrombus ◽

Portal Vein Branch ◽

Peripheral Dose ◽

Multivariable Analyses ◽

Treatment Responses ◽

Grade 3

e15646 Background: Patients with hepatocellular carcinoma (HCC) accompanied with portal vein tumor thrombus (PVTT) have a poor prognosis. Although transarterial chemoembolization (TACE) plus sorafenib (TACE-S) could lead to an improved survival than TACE alone in HCC patients with first- or second-branch PVTT (branch PVTT), the survival was very limited. We compared the safety and efficacy of TACE plus Iodine125 brachytherapy (TACE-I) with TACE-S in patients with unresectable HCC and branch PVTT. Methods: The medical records of consecutive patients with HCC and branch PVTT who underwent TACE-I (TACE-I group) or TACE-S (TACE-S group) from January 2015 to December 2017 were retrospectively evaluated. Iodine125 seeds were implanted into the PVTT under CT guidance 3-5 days after the initial TACE. The matched peripheral dose of Iodine125 brachytherapy was set to be 120-140 Gy. Sorafenib was administered 400 mg twice daily. Outcomes of patients who underwent TACE-I, including adverse events, treatment responses, time to progression (TTP), and overall survival (OS), were compared with those of patients who underwent TACE-S. Results: One hundred and twenty patients were included in the analysis; 62 patients underwent TACE-I and 58 underwent TACE-S. The overall incidence of adverse events was significantly lower in TACE-I group than in TACE-S group (58.1% vs. 93.1%, P < .001), and incidence of grade 3 or higher adverse events also was significantly lower in TACE-I group than in TACE-S group (3.2% vs. 27.6%, P < .001). PVTT OR rates at 12 weeks (58.1% vs. 13.8%, P < .001) and at 24 weeks after the treatment (68.9 % vs. 10.9%, P < .001) in TACE-I group were higher than those in TACE-S group. TACE-I led to significantly longer TTP (median, 11.2 months vs. 6.2 months, P < .001) and OS (median, 20.9 months vs. 14.0 months, P < .001) than TACE-S. In uni- and multivariable analyses, TACE-I treatment, PVTT extent, tumor size ≥10 cm, PVTT OR at 12 weeks, and intrahepatic tumor OR at 12 weeks were independent prognostic factors for OS. Conclusions: TACE-I had less side effects and may improve OS than TACE-S for HCC patients with branch PVTT.

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Transarterial Chemoembolization (TACE) Combined with Sorafenib in Treatment of HBV Background Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propensity Score Matching Study

BioMed Research International ◽

10.1155/2019/2141859 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Jia Yuan ◽

Xin Yin ◽

Bei Tang ◽

Hui Ma ◽

Lan Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Propensity Score ◽

Combination Therapy ◽

Portal Vein ◽

Propensity Score Matching ◽

Transarterial Chemoembolization ◽

Tumor Thrombus ◽

Portal Vein Tumor Thrombus ◽

Rank Test

Objectives. Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains a challenge in management. Transarterial chemoembolization (TACE) has been used for patients with PVTT but efficiency was limited with a median overall survival of 4 to 6.1 months. The aim of this study is to evaluate the efficiency of TACE combined with sorafenib in HBV background HCC with PVTT. Methods. A total of 498 patients were enrolled in the study including 69 patients who received TACE combined with sorafenib and 429 patients treated with TACE alone between January 1st, 2008, and April 30st, 2014. Using the 1:2 propensity score matching, 138 well-balanced patients were enrolled. Overall survival (OS) was compared between the two groups. The Kaplan-Meier method was used to evaluate the OS, and the differences between groups were analyzed with a log-rank test. Results. TACE combined with sorafenib improved the OS of the patients compared with TACE alone (13.0 vs 6.0 months, p<0.001). After propensity score matching, the median OS of combination therapy and TACE were 13.0 and 7.0 months, respectively (p=0.001). Subgroup analysis revealed that the patients younger than 60 years old, male patients, AFP more than 400ng/ml, tumor size more than 5cm, or type III/IV PVTT had OS benefits from TACE combined with sorafenib. Conclusions. Compared with TACE therapy alone, TACE combined with sorafenib could improve OS in HBV background HCC patients with PVTT. The patients who are younger, male, or with more tumor burden may benefit more from combination therapy.

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Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study

BMC Anesthesiology ◽

10.1186/s12871-020-01111-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiao-Yan Meng ◽

Xiu-Ping Zhang ◽

Zhe Sun ◽

Hong-Qian Wang ◽

Wei-Feng Yu

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Portal Vein ◽

Tumor Thrombus ◽

Cox Regression ◽

Cancer Recurrence ◽

Portal Vein Tumor Thrombus ◽

Cox Regression Analysis ◽

The Impact ◽

Underlying Pathophysiology

Abstract Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

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Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2015.64.8808 ◽

2016 ◽

Vol 34 (14) ◽

pp. 1660-1668 ◽

Cited By ~ 48

Author(s):

Thomas Powles ◽

Mark R. Lackner ◽

Stéphane Oudard ◽

Bernard Escudier ◽

Christy Ralph ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Adverse Events ◽

Renal Cell ◽

Response Rate ◽

Objective Response ◽

Mammalian Target Of Rapamycin ◽

Hypoxia Inducible Factor ◽

Progression Free Survival ◽

Free Survival

Purpose To the best of our knowledge, this study is the first to compare dual inhibition of PI3K/mammalian target of rapamycin (mTOR) by apitolisib (GDC-0980) against single inhibition of mTORC1 by everolimus in metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC who progressed on or after vascular endothelial growth factor–targeted therapy were randomly assigned to apitolisib 40 mg once per day or to everolimus 10 mg once per day. End points included progression-free survival, safety, overall survival, and objective response rate. Biomarker assessments were conducted. Results Eighty-five patients were randomly assigned. After 67 events, stratified analysis revealed that median progression-free survival was significantly shorter for apitolisib than for everolimus (3.7 v 6.1 months; hazard ratio, 2.12 [95% CI, 1.23 to 3.63; P < .01]); apitolisib was not favored in any stratification subgroup. Median overall survival was not significantly different but trended in favor of everolimus (16.5 v 22.8 months; hazard ratio, 1.77 [95% CI, 0.97 to 3.24; P = .06]). The objective response rate was 7.1% for apitolisib and 11.6% for everolimus. Patients administered apitolisib with a greater incidence of grade 3 to 4 adverse events were more likely to discontinue treatment (31% v 12% for everolimus). No drug-related deaths were observed. Apitolisib in comparison with everolimus was associated with substantially more high-grade hyperglycemia (40% v 9%) and rash (24% v 2%). Apitolisib pharmacokinetics suggested a relationship between exposure, and rash and hyperglycemia. Retrospective biomarker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not with apitolisib. High hypoxia-inducible factor 1α protein expression was associated with better outcome in both arms. Conclusion This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than was everolimus in mRCC, likely because full blockade of PI3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and hypoxia-inducible factor 1α expression may be predictive of an mTOR inhibitor benefit, although prospective validation is required.

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Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Transarterial Chemoembolization and Sorafenib vs.125Iodine Implantation

Frontiers in Oncology ◽

10.3389/fonc.2021.806907 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hong-Tao Hu ◽

Jun-Peng Luo ◽

Guang-Shao Cao ◽

Zhen Li ◽

Ming Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Portal Vein ◽

Transarterial Chemoembolization ◽

Clinical Status ◽

Objective Response ◽

Clinical Trial Registration ◽

Ct Guided ◽

Seed Implantation ◽

Sorafenib Group

Background and AimsThis study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT).MethodsThis prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death.ResultsThis study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105–10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519–18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively.ConclusionsThis study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events.Clinical Trial RegistrationChinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.

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Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma

British Journal of Radiology ◽

10.1259/bjr.20190407 ◽

2020 ◽

Vol 93 (1110) ◽

pp. 20190407 ◽

Cited By ~ 2

Author(s):

Atsushi Hori ◽

Ryosuke Ohira ◽

Tomoyuki Nakamura ◽

Yasushi Kimura ◽

Shota Ueda ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Adverse Events ◽

Objective Response ◽

Evaluation Criteria ◽

Reduction Rate ◽

End Point ◽

Promising Treatment ◽

Grade 3 ◽

Arterial Chemoembolization

Objective: To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC). Methods: Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1–3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand. Results: TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively. Conclusion: Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC. Advances in knowledge: Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.

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Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)

Journal of Clinical Oncology ◽

10.1200/jco.19.03054 ◽

2020 ◽

Vol 38 (25) ◽

pp. 2916-2925 ◽

Cited By ~ 4

Author(s):

Jean-Jacques Grob ◽

Rene Gonzalez ◽

Nicole Basset-Seguin ◽

Olga Vornicova ◽

Jacob Schachter ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Adverse Events ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Cutaneous Squamous Cell Carcinoma ◽

Free Survival ◽

Duration Of Response

PURPOSE Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort—locally advanced and R/M—phase II KEYNOTE-629 study. PATIENTS AND METHODS Patients with R/M cSCC not amenable to surgery or radiation received pembrolizumab 200 mg every 3 weeks. The primary end point was objective response rate per RECIST v1.1. Secondary end points were duration of response, disease control rate, progression-free survival, overall survival, and safety. RESULTS At data cutoff (April 8, 2019), median follow-up of 105 enrolled patients in the R/M cohort was 11.4 months (range, 0.4 to 16.3 months). Objective response rate was 34.3% (95% CI, 25.3% to 44.2%; 4 complete responses, 32 partial responses), and disease control rate was 52.4% (95% CI, 42.4% to 62.2%). Median duration of response was not reached (range, 2.7 to 13.1+ months; ‘+’ refers to ongoing response at data cutoff). Median progression-free survival was 6.9 months (95% CI, 3.1 months to 8.5 months). Median overall survival was not reached (95% CI, 10.7 months to not reached). Treatment-related adverse events occurred in 66.7% of patients (n = 70), the most common of which were pruritus (n = 15; 14.3%), asthenia (n = 14; 13.3%), and fatigue (n = 13; 12.4%). Grade 3 to 5 treatment-related adverse events occurred in 5.7% (n = 6) of patients. One patient died of treatment-related cranial nerve neuropathy. CONCLUSION Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with R/M cSCC, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.

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