scholarly journals Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

2017 ◽  
Vol 35 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Sandra P. D’Angelo ◽  
James Larkin ◽  
Jeffrey A. Sosman ◽  
Celeste Lebbé ◽  
Benjamin Brady ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Programmed Death ◽  
Programmed Death 1

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Efficacy and safety of capecitabine plus oxaliplatin (XELOX) as the perioperative treatment of patients with potentially resectable liver-only metastases from colorectal cancer: A single arm, open-label, multicenter phase II trial (ML22298; NCT00997685).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 777-777
Author(s):  
Feng Lin ◽  
Guoxin Li ◽  
Zhonghua Chu ◽  
Chunyi Hao ◽  
Mingqing Chen ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Free Survival ◽  
Perioperative Treatment ◽  
Post Operation ◽  
Secondary Endpoints ◽  
Tumor Remission

777 Background: Surgical resection can improve survival of patients with resectable colorectal liver metastases (CLMs). Here, we investigatedthe efficacy and safety of XELOX as perioperative treatment for patients with potentially resectable CLM. Methods: Patients with potentially resectable liver-only metastases from CRC were enrolled. The primary endpoint of this study was progression-free survival (PFS); and the secondary endpoints included objective response rate (ORR), R0 resection rate, overall survival (OS) and safety profile of perioperative treatment of XELOX. Eligible patients were treated with XELOX (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 b.i.d. for 14 days every 3 weeks). Tumor remission was assessed by CT after 6 weeks (2 cycles) of chemotherapy. Resectability of CLM was assessed by CT after 12 weeks (4 cycles) of chemotherapy. Adjuvant chemotherapy using XELOX was started within 8 weeks after hepatectomy. Results: Thirty patients (17 males and 13 females) were enrolled from 10 medical sites between January 2010 and October 2011, with median age of 57.5 years (range: 32-77). Median PFS was 336 days (95% CI: 173~385), and median OS was 912 days (95% CI: 516~1332). The ORR was 40% (12/30). The conversion rate from unresectable to resectable was 43.3% (13/30). Among these 11 patients who had received surgery (2 had withdrawn consent), 10 (90.9%) had received R0 resection. Subgroup analysis shows that patients who had received hepatectomy had longer median PFS [95% CI] (382 days [210~518] vs. 173 days [111~337], p = 0.0268) and median OS [95% CI] (1332 [721~NA] vs. 516 [295~1046], p = 0.005). There were 4 patients with post-operation complications of ascites and/or hydrothorax, and 3 patients had early chemotherapy termination due to drug-related AEs, including leukopenia, hepatotoxicity and diarrhea. Conclusions: Perioperative chemotherapy of XELOX is an option for patients with potentially resectable CLM due to the effect in prolonging PFS and OS, as well as the manageable toxicities and post-operation complications. Clinical trial information: NCT00997685.

The efficacy and safety of lenvatinib in patients with intermediate-stage hepatocellular carcinoma: A nationwide multicenter study in Japan.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 548-548
Author(s):  
Kaoru Tsuchiya ◽  
Masayuki Kurosaki ◽  
Azusa Sakamoto ◽  
Hiroyuki Marusawa ◽  
Chikara Ogawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multicenter Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Intermediate Stage ◽  
Median Number ◽  
Observation Time ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Modified Recist

548 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. We conducted a nationwide multicenter study and especially focused on the efficacy and safety in the patients with intermediate-stage u-HCC. Methods: A total of 240 patients received LEN from March 2018 at 15 sites in Japan was enrolled. Tumour assessments in accordance with modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Results: In this study, 88 of 240 (36.7%) patients were BCLC stage B. Among them 76 (86.3%) patients received TACE before LEN and the median number of TACE was 2 (1-10). Only 4 patients were TKI experienced and other 84 (95.5%) patients received LEN as a 1st line therapy. The median pretreatment ALBI score was -2.35 and 75 (85.2%) patients were Child-Pugh A. In this cohort, 73 (83.0%) patients were beyond up-to-seven criteria and the median pretreatment AFP was 38.2 (2-12870) ng/mL. The median observation time was 8.5 months and 16 patients died. The median progression free survival was 8.7 months, and the median overall survival (OS) was not reached. Objective response rate (ORR) and disease control rate (DCR) were 48.5% and 80.3%. AFP decrease ( > 20%) after 1 month was observed in 52 (59.0%) patients. Child-Pugh B patients (n = 13) had significantly shorter OS than Child-Pugh A (p = 0.02) and median OS in Child-Pugh B patients was 8.8 months. The patients received > 6 times TACE before LEN had significantly shorter OS than patients received ≤ 6 times TACE (p = 0.02). Additional TACE was performed in 8 patients and The median time of restarting LEN was 19 days. The median ALBI score before additional TACE, Day 1 after TACE and Day 28 after TACE were -2.38, -2.07, and -2.36.There was no severe adverse event associated with additional TACE. The median duration of LEN in patients treated with LEN and additional TACE was 8.5 months. Conclusions: The ORR and DCR of LEN in Child-Pugh A patients with intermediate-stage HCC were 46.6% and 79.3%. The therapeutic strategies for intermediate-stage HCC should be discussed based on the liver function, tumor states, and treatment course about TACE.

scholarly journals Prognostic implications of PD-L1 expression in patients with angiosarcoma

2021 ◽  
pp. FSO691
Author(s):  
Jii Bum Lee ◽  
Beung-Chul Ahn ◽  
Seung Hyun Kim ◽  
Young Han Lee ◽  
Jung Woo Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Limited Data ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Median Progression Free Survival ◽  
Programmed Death ◽  
Prognostic Implications

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.

scholarly journals Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study

2019 ◽  
Vol 37 (23) ◽  
pp. 1997-2007 ◽  
Author(s):  
Radhakrishnan Ramchandren ◽  
Eva Domingo-Domènech ◽  
Antonio Rueda ◽  
Marek Trněný ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Classic Hodgkin Lymphoma ◽  
Immune Mediated ◽  
Programmed Death

PURPOSE Nivolumab, an anti–programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

A randomized phase II study of chemoradiation (CRT) +/- nivolumab (Nivo) with sequential safety evaluations of Nivo +/- lirilumab (Liri) or ipilumumab (Ipi) concomitant with (C) RT in intermediate (IR) and high-risk (HR) head and neck squamous cell carcinoma (HNSCC) (RTOG 3504, NCT02764593).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS6097-TPS6097 ◽  
Author(s):  
Maura L. Gillison ◽  
Robert L. Ferris ◽  
Qiang Zhang ◽  
A. Dimitrios Colevas ◽  
Loren K. Mell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Safety Evaluation ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Programmed Death ◽  
Secondary Endpoints ◽  
Platinum Refractory ◽  
Programmed Death 1

TPS6097 Background: Nivolumab (Nivo), a monoclonal antibody to the programmed death-1 (PD-1) immune checkpoint receptor, improved overall survival (OS) for patients (pts) with platinum-refractory, recurrent/metastatic HNSCC compared with standard therapy. A placebo controlled phase IIR trial was designed to investigate the hypothesis that Nivo added to platinum-based CRT will improve progression free survival (PFS) for pts with newly diagnosed IR/HR HNSCC. Methods: Eligibility includes IR HNSCC (p16+, oropharynx T1-2N2b-N3/T3-4N0-3, > 10 pack-years (pys) or T4N0-N3, T1-3N3 ≤ 10 pys) and HR HNSCC (oral cavity, larynx, hypopharynx, or p16(-) oropharynx, stage T1-2N2a-N3 or T3-4N0-3). After safety evaluation in 8 evaluable pts, 176 pts will be randomized (1:1) to cisplatin (40 mg/m2/week X 7) with radiation (IMRT, 70 Gy in 7 weeks) +/- Nivo/placebo (240 mgs q14 days X 5, then 480 mgs q28 X3). Primary endpoint is PFS. Secondary endpoints include OS, acute and chronic toxicity, quality of life and biomarkers (tumor PD-L1 expression; E6/7 seroreactivity and frequency of functional circulating and intraumoral T cells). Parallel with Phase IIR are sequential safety evaluations (see Table) in platinum eligible and ineligible ( > 70 years; ≥3 grade neuropathy; ≥2 hearing loss; or CrCl < 60 ml/min) cohorts (N = 10-20) of Nivo +/- Liri (anti-KIR) or Ipi (anti-CTLA4) concomitant with RT alone, cisplatin-RT or cetuximab-RT platforms followed by 3 months of adjuvant immunotherapy. The primary endpoint is safety and feasibility. With 8 evaluable pts, the probability of treatment assessed as toxic is > 78% when the true toxicity rate is > 45% and treatment assessed tolerable is > 80% if the true toxicity rate is < 20%. Clinical trial information: NCT02764593. [Table: see text]

scholarly journals The efficacy and safety of apatinib treatment for patients with advanced or recurrent biliary tract cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caiyun Nie ◽  
Huifang Lv ◽  
Yishu Xing ◽  
Beibei Chen ◽  
Weifeng Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Tract Cancer ◽  
Systemic Therapies

Abstract Introduction The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8–6.8) and 6.2 months (95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

scholarly journals Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma

Blood ◽  
2020 ◽  
Author(s):  
Philippe Armand ◽  
Ann MH Janssens ◽  
Giuseppe Gritti ◽  
John Radford ◽  
John M Timmerman ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Tumor Associated Macrophage ◽  
Phase 2 Trial ◽  
Programmed Death ◽  
Phase 2 Study ◽  
Programmed Death 1

Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to evaluate further its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least two prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary endpoint was objective response rate (ORR) assessed by independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4/92). Median PFS was 2.2 months (95% confidence interval [CI], 1.9-3.6). Median DOR was 11 months (95% CI, 8-14). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than non-responders, but no significant differences in PD-1 or PD-L1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.

scholarly journals The Efficacy and Safety of Apatinib Treatment for Patients with Advanced or Recurrent Biliary Tract Cancer: A Retrospective Study

2020 ◽  
Author(s):  
Caiyun Nie ◽  
Huifang Lv ◽  
Yishu Xing ◽  
Beibei Chen ◽  
Weifeng Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Tract Cancer ◽  
Systemic Therapies

Abstract Background The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer(BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy, including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. 6 patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months(95%CI = 1.8–6.8) and 6.2 months(95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

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