scholarly journals The efficacy and adverse events of anlotinib plus PD-1 inhibitor for metastatic solid tumors

2021 ◽  
Author(s):  
Hao Lin ◽  
Tao Liu ◽  
Xinli Zhou ◽  
Xiaohua Liang
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Kaplan Meier ◽  
Hemorrhagic Events ◽  
Tumor Immune Microenvironment

Abstract Background Several antiangiogenic tyrosine kinase inhibitors (TKIs) have the potential to modulate the tumor immune microenvironment and improve immunotherapy effect Of these, anlotinib has demonstrated antitumor efficacy in clinical trials. However, its role in immune regulation and the potential synergistic antitumor effect of its combination with PD-1 inhibitor remain unclear. This study investigated the efficacy and adverse events (AEs) of the combination of anlotinib and PD-1 inhibitor for solid tumors in real-world settings. Methods This retrospective study included patients with metastatic solid tumors treated with anlotinib plus PD-1 inhibitor at Huashan hospital, Fudan University between October 1, 2018 and August 31, 2020. The objective response rate was assessed using the response evaluation criteria in solid tumors v1.1. Descriptive statistics were performed using the Kaplan–Meier method, and any AEs were noted. Results Partial response was achieved in 13 patients, and 8 patients showed stable disease, representing a response rate of 43.3% and a disease control rate of 70%. The median progression-free survival was 3.8 months. Although AEs were observed in 50% of patients, most of them were Grades 1–2 and well tolerated. The most common AEs were thrombocytopenia (16%), thromboembolic or hemorrhagic events (16%), and rash (13%). Conclusions Anlotinib plus PD-1 inhibitor is an alternative salvage treatment choice in metastatic solid tumors with Favorable efficacy and tolerable toxicities.

Chemosaturation durch perkutane hepatische Perfusion mit Melphalan bei hepatisch metastasiertem Aderhautmelanom: eine Überlebens- und Sicherheitsanalyse

2021 ◽  
Vol 42 (08) ◽  
pp. 576-584
Author(s):  
Cornelia Lieselotte Angelika Dewald ◽  
Jan B. Hinrichs ◽  
Lena Sophie Becker ◽  
Sabine Maschke ◽  
Timo C. Meine ◽  
...  
Keyword(s):  
Disease Control ◽  
Solid Tumors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Evaluation Criteria ◽  
Progressionsfreies Überleben ◽  
Response Evaluation ◽  
Ischämischer Insult ◽  
Kaplan Meier ◽  
Response Evaluation Criteria

Ziel Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Material und Methoden Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. Ergebnisse 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Schlussfolgerung Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit.

Comparing the clinical efficacies of anti-PD-1 antibody monotherapy and anti-PD-1 and anti-CTLA-4 combination therapy as first-line immunotherapy in Japanese advanced acral melanoma: A retrospective, multicenter study (JAMP-neo study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9542-9542
Author(s):  
Yasuhiro Nakamura ◽  
Yukiko Kiniwa ◽  
Hiroshi Kato ◽  
Osamu Yamasaki ◽  
Takeo Maekawa ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Efficacy ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
First Line ◽  
Acral Melanoma ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Clinical Records

9542 Background: Anti-PD-1 antibody monotherapy (PD1) has been commonly used for patients with advanced acral melanoma (AM). However, recent studies have demonstrated the limited clinical efficacy of PD1 in AM compared to non-acral cutaneous melanoma, particularly in nail apparatus melanoma. Although advanced AM patients are strong candidates for first-line anti-PD-1 and anti-CTLA-4 combination therapy (PD1+CTLA4), data on the clinical efficacy of PD1+CTLA4 in AM are lacking. Thus, we aimed to compare the clinical efficacies of PD1+CTLA4 and PD1 in Japanese advanced AM patients. Methods: We retrospectively reviewed the clinical records of advanced AM patients treated with PD1+CTLA4 or PD1 as first-line immunotherapy at 23 Japanese institutions. Clinical response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 192 patients (median age, 72 years) with advanced AM (palm and sole melanoma, 135; nail apparatus melanoma, 57) were included in the study. PD1+CTLA4 and PD1 were used as first-line immunotherapy in 39 and 153 patients, respectively. The baseline demographics and characteristics were similar between the PD1+CTLA4 and PD1 groups, except for age (median age 67.3 vs. 73.2; P = 0.005). The objective response rate (ORR) in PD1+CTLA4 was significantly higher than that of the PD1 group (38.5% vs. 16.3%; P = 0.047). The median progression-free survival (PFS) and overall survival (OS) in the PD1+CTLA4 group tended to be longer than those of the PD1 group, but the differences were not significant (median PFS 7.3 months vs. 4.5 months; P = 0.19, median OS 43.6 months vs. 18.2 months; P = 0.19). In the subgroup analysis of the palm and sole melanoma cohorts, no significant differences in ORR, PFS, and OS were observed between the PD1+CTLA4 and PD1 groups (ORR 31% vs. 20.8%; P = 0.67, median PFS 5.3 months vs. 5.9 months; P = 0.87, median OS not reached vs. 22.3 months; P = 0.66). Meanwhile, the nail apparatus melanoma cohort in the PD1+CTLA4 group exhibited significantly higher ORR, and longer PFS and OS than the PD1 group (ORR 60% vs 6.1%; P < 0.001; median PFS 19.6 months vs 3.8 months; P = 0.008, median OS 43.6 months vs 13.5 months; P = 0.049). Due to immune-related adverse events in all cohorts, the treatment cessation rate was higher in the PD1+CTLA4 group than the PD1 group (59% vs. 11.8%). Conclusions: PD1+CTLA4 was clinically more efficacious than PD 1 in advanced AM patients. Notably, advanced nail apparatus melanoma patients were strong candidates for first-line PD1+CTLA4.

scholarly journals Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 952 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Satoru Hagiwara ◽  
Tomoko Aoki ◽  
Tomohiro Minami ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Treatment Discontinuation ◽  
The Impact ◽  
Group 1

Background: This study investigated the impact of baseline liver function according to the Child–Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular carcinoma treated with lenvatinib. Methods: A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child–Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child–Pugh score 5 and ALBI grade 1 (group 1), (2) Child–Pugh score 5 and ALBI grade 2 (group 2), (3) Child–Pugh score 6 (group 3), and (4) Child–Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events. Results: Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (p < 0.05 and p < 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (p < 0.05 and p < 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (p < 0.01). Conclusions: Patients with Child–Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment.

scholarly journals TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huanhuan Yin ◽  
Wei Guo ◽  
Xiangling Sun ◽  
Ruili Li ◽  
Cuihua Feng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Survival Time ◽  
Response Rate ◽  
Multivariate Analyses ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

scholarly journals 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

2016 ◽  
Vol 34 (14) ◽  
pp. 1660-1668 ◽  
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.

Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

2004 ◽  
Vol 22 (23) ◽  
pp. 4762-4771 ◽  
Author(s):  
Maria A. Kouvaraki ◽  
Jaffer A. Ajani ◽  
Paulo Hoff ◽  
Robert Wolff ◽  
Douglas B. Evans ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response To Treatment ◽  
Rank Test ◽  
Median Response ◽  
Log Rank Test

Purpose The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS). Patients and Methods Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee. Results Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P < .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS. Conclusion Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.

scholarly journals Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors

2021 ◽  
pp. 756-766
Author(s):  
Yuki Takeyasu ◽  
Hitomi S. Okuma ◽  
Yuki Kojima ◽  
Tadaaki Nishikawa ◽  
Maki Tanioka ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Alk Rearrangement ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
Treatment Interruptions ◽  
Alk Positive

PURPOSE Anaplastic lymphoma kinase ( ALK) rearrangement is a well-known driver oncogene in non–small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors. PATIENTS AND METHODS Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression. RESULTS We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. CONCLUSION This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

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

2020 ◽  
Vol 38 (25) ◽  
pp. 2916-2925 ◽  
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.

A clinical study to evaluate the efficacy and safety of docetaxel with ribavirin in patients with progressive castration resistant prostate cancer who have previously received docetaxel alone.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14010-e14010 ◽  
Author(s):  
Takeo Kosaka ◽  
Takahiro Maeda ◽  
Toshiaki Shinojima ◽  
Hirohiko Nagata ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Clinical Study ◽  
Adverse Events ◽  
Disease Progression ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Grade 3

e14010 Background: We have previously reported a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting cancer stemness related gene network and identified ribavirin as a candidate drug for overcoming docertaxel resistant castration resistant prostate cancer.This non-randamized and open-labelled pilot clinical study explored the safety and efficacy of ribavirin, anti-virus drug, in combination with docetaxel in patients with progressive CRPC. Methods: In this clinical study, patients received intravenous docetaxel 60-70 mg/mm2 on day 1 of 3-6 weeks cycles plus Ribavirin 600 mg twice daily. The primary endopoint was safety, PSA response and objective response rate. Secondary end ponts included health-related quality of life overall survival.Patients with progressive CRPC based on PSA and/or radiographic criteria, PS 0-1, normal renal and hepatic function were eligible. Results:Five patients were enrolled in this study. Medium age was 73. Median serum PSA concentration was 53.1 ng/ml (range: 5.1-370.5).The median cycle and total dose of docetaxel received before the study was 31 cycles and 3625 mg, respectively. 80% of patients who had disease progression during docetaxel treatment. The median time from last docetaxel dose to disease progression before the participation was 1.5 months.Safety: Medium number of treatment cycles were 7 (range: 3-8) cycles. Grade 3/4 adverse events requiring dose modification were not observed. Grade 3 anemia and neutropenia were seen in two patients. Common adverse events were less than Grade 2. Efiicacy: 3 (60%) had some degree of PSA decline and 2 (40%) had a decline of ≧30 %. Median follow-up was 10.0 month. Median progression free survival was 6 month. Conclusions: This combination was well tolerated with promising response rate, justifying further investigation in docetaxel resistant CRPC. Clinical trial information: UMIN000012521.

scholarly journals Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study

2020 ◽  
Vol 8 (1) ◽  
pp. e000331 ◽  
Author(s):  
Yana G Najjar ◽  
Kristina Navrazhina ◽  
Fei Ding ◽  
Roma Bhatia ◽  
Katy Tsai ◽  
...  
Keyword(s):  
Adverse Events ◽  
Uveal Melanoma ◽  
Progressive Disease ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Prior Therapy ◽  
Kaplan Meier ◽  
Academic Medical

BackgroundUveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined.MethodsWe conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology.Results89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%).ConclusionsDual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.

Sign in / Sign up

Export Citation Format

Share Document