Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Melanoma: HELP
Articles by Amita Patnaik
Based on 7 articles published since 2010
(Why 7 articles?)
||||

Between 2010 and 2020, A. Patnaik wrote the following 7 articles about Melanoma.
 
+ Citations + Abstracts
1 Clinical Trial Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. 2018

Robert, Caroline / Ribas, Antoni / Hamid, Omid / Daud, Adil / Wolchok, Jedd D / Joshua, Anthony M / Hwu, Wen-Jen / Weber, Jeffrey S / Gangadhar, Tara C / Joseph, Richard W / Dronca, Roxana / Patnaik, Amita / Zarour, Hassane / Kefford, Richard / Hersey, Peter / Zhang, Jin / Anderson, James / Diede, Scott J / Ebbinghaus, Scot / Hodi, F Stephen. ·Caroline Robert, Gustave Roussy Cancer Campus and Paris Sud University, Villejuif Paris-Sud, France · Antoni Ribas, University of California, Los Angeles · Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles · Adil Daud, University of California, San Francisco, San Francisco, CA · Jedd D. Wolchok, Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY · Anthony M. Joshua, The Princess Margaret Cancer Centre, Toronto, Ontario, Canada · Wen-Jen Hwu, The University of Texas MD Anderson Cancer Center, Houston · Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX · Jeffrey S. Weber, H Lee Moffitt Cancer Center, Tampa · Richard W. Joseph, Mayo Clinic Cancer Center-Florida, Jacksonville, FL · Tara C. Gangadhar, Abramson Cancer Center at the University of Pennsylvania, Philadelphia · Hassane Zarour, UPMC Hillman Cancer Center, Pittsburgh, PA · Roxana Dronca, Mayo Clinic, Rochester, MN · Richard Kefford, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead · Melanoma Institute Australia, Wollstonecraft · and Macquarie University, MQ Health, Health Sciences Centre · Peter Hersey, University of Sydney, Sydney, New South Wales, Australia · Jin Zhang, James Anderson, Scott J. Diede, and Scot Ebbinghaus, Merck & Co., Inc., Kenilworth, NJ · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA. ·J Clin Oncol · Pubmed #29283791.

ABSTRACT: Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

2 Clinical Trial Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. 2016

Daud, Adil I / Wolchok, Jedd D / Robert, Caroline / Hwu, Wen-Jen / Weber, Jeffrey S / Ribas, Antoni / Hodi, F Stephen / Joshua, Anthony M / Kefford, Richard / Hersey, Peter / Joseph, Richard / Gangadhar, Tara C / Dronca, Roxana / Patnaik, Amita / Zarour, Hassane / Roach, Charlotte / Toland, Grant / Lunceford, Jared K / Li, Xiaoyun Nicole / Emancipator, Kenneth / Dolled-Filhart, Marisa / Kang, S Peter / Ebbinghaus, Scot / Hamid, Omid. ·Adil I. Daud, University of California, San Francisco, San Francisco · Antoni Ribas, University of California, Los Angeles · Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles · Charlotte Roach and Grant Toland, Dako North America, Carpinteria, CA · Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY · Wen-Jen Hwu, The University of Texas MD Anderson Cancer Center, Houston · Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX · Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa · Richard Joseph, Mayo Clinic, Jacksonville, FL · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Tara C. Gangadhar, Abramson Cancer Center at the University of Pennsylvania, Philadelphia · Hassane Zarour, University of Pittsburgh, Pittsburgh, PA · Roxana Dronca, Mayo Clinic, Rochester, MN · Jared K. Lunceford, Xiaoyun Nicole Li, Kenneth Emancipator, Marisa Dolled-Filhart, S. Peter Kang, and Scot Ebbinghaus, Merck & Co, Kenilworth, NJ · Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif, France · Anthony M. Joshua, Princess Margaret Cancer Centre, Toronto, ON, Canada · Richard Kefford, Crown Princess Mary Cancer Centre, Westmead Hospital and Melanoma Institute Australia · Richard Kefford, Macquarie University · and Richard Kefford and Peter Hersey, University of Sydney, Sydney, NSW, Australia. ·J Clin Oncol · Pubmed #27863197.

ABSTRACT: Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score ≥ 2 (membranous staining in ≥ 1% of cells) was considered positive. Results Of 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1-positive tumors. Demographic and staging variables were equally distributed among PD-L1-positive and -negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed ( P < .001 for each). Objective response rate was 8%, 12%, 22%, 43%, 57%, and 53% for MEL 0, 1, 2, 3, 4, and 5, respectively. Conclusion PD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, PFS, and OS; however, patients with PD-L1-negative tumors may also achieve durable responses.

3 Clinical Trial Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. 2016

Ribas, Antoni / Hamid, Omid / Daud, Adil / Hodi, F Stephen / Wolchok, Jedd D / Kefford, Richard / Joshua, Anthony M / Patnaik, Amita / Hwu, Wen-Jen / Weber, Jeffrey S / Gangadhar, Tara C / Hersey, Peter / Dronca, Roxana / Joseph, Richard W / Zarour, Hassane / Chmielowski, Bartosz / Lawrence, Donald P / Algazi, Alain / Rizvi, Naiyer A / Hoffner, Brianna / Mateus, Christine / Gergich, Kevin / Lindia, Jill A / Giannotti, Maxine / Li, Xiaoyun Nicole / Ebbinghaus, Scot / Kang, S Peter / Robert, Caroline. ·Division of Hematology and Oncology, University of California-Los Angeles, Los Angeles. · Department of Hematology/Oncology, The Angeles Clinic and Research Institute, Los Angeles, California. · Department of Hematology/Oncology, University of California-San Francisco, San Francisco. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital and Melanoma Institute Australia, Sydney, Australia7Department of Clinical Medicine, Macquarie University, Sydney, Australia. · Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · Department of Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio. · Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Division of Hematology and Oncology, Abramson Cancer Center at the University of Pennsylvania, Philadelphia. · Department of Medicine, University of Sydney, Sydney, Australia. · Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota. · Department of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida. · Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. · Department of Hematology/Oncology, Massachusetts General Hospital, Boston. · Department of Medical Oncology, Gustave-Roussy Cancer Campus and Paris Sud University, Villejuif Paris-Sud, France. · Department of Clinical Oncology, Merck & Co, Inc, Kenilworth, New Jersey. · BARDS, Merck & Co, Inc, Kenilworth, New Jersey. ·JAMA · Pubmed #27092830.

ABSTRACT: IMPORTANCE: The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab. OBJECTIVE: To characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Cutoff dates were April 18, 2014, for safety analyses and October 18, 2014, for efficacy analyses. EXPOSURES: Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision. MAIN OUTCOMES AND MEASURES: The primary end point was confirmed objective response rate (best overall response of complete response or partial response) in patients with measurable disease at baseline per independent central review. Secondary end points included toxicity, duration of response, progression-free survival, and overall survival. RESULTS: Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33% [95% CI, 30%-37%]) and in 60 of 133 treatment-naive patients (45% [95% CI, 36% to 54%]). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% (95% CI, 31%-39%) in the total population and 52% (95% CI, 43%-60%) among treatment-naive patients. Median overall survival in the total population was 23 months (95% CI, 20-29) with a 12-month survival rate of 66% (95% CI, 62%-69%) and a 24-month survival rate of 49% (95% CI, 44%-53%). In treatment-naive patients, median overall survival was 31 months (95% CI, 24 to not reached) with a 12-month survival rate of 73% (95% CI, 65%-79%) and a 24-month survival rate of 60% (95% CI, 51%-68%). Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths. CONCLUSIONS AND RELEVANCE: Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01295827.

4 Clinical Trial Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab. 2016

Hodi, F Stephen / Hwu, Wen-Jen / Kefford, Richard / Weber, Jeffrey S / Daud, Adil / Hamid, Omid / Patnaik, Amita / Ribas, Antoni / Robert, Caroline / Gangadhar, Tara C / Joshua, Anthony M / Hersey, Peter / Dronca, Roxana / Joseph, Richard / Hille, Darcy / Xue, Dahai / Li, Xiaoyun Nicole / Kang, S Peter / Ebbinghaus, Scot / Perrone, Andrea / Wolchok, Jedd D. ·F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Wen-Jen Hwu, The University of Texas MD Anderson Cancer Center, Houston · Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX · Richard Kefford, Westmead Hospital, Melanoma Institute Australia, and Macquarie University · Peter Hersey, University of Sydney, Sydney, Australia · Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa · Richard Joseph, Mayo Clinic, Jacksonville, FL · Adil Daud, University of California San Francisco, San Francisco · Omid Hamid, The Angeles Clinic and Research Institute · Antoni Ribas, University of California Los Angeles, Los Angeles, CA · Caroline Robert, Gustave-Roussy and Paris-Sud University, Villejuif-Paris-Sud, France · Tara C. Gangadhar, Abramson Cancer Center, Philadelphia, PA · Anthony M. Joshua, Princess Margaret Hospital, Toronto, Ontario, Canada · Roxana Dronca, Mayo Clinic, Rochester, MN · Darcy Hille, Dahai Xue, Xiaoyun Nicole Li, S. Peter Kang, Scot Ebbinghaus, and Andrea Perrone, Merck, Kenilworth, NJ · and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY. ·J Clin Oncol · Pubmed #26951310.

ABSTRACT: PURPOSE: We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). PATIENTS AND METHODS: Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. RESULTS: Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). CONCLUSION: Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

5 Clinical Trial Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. 2014

Robert, Caroline / Ribas, Antoni / Wolchok, Jedd D / Hodi, F Stephen / Hamid, Omid / Kefford, Richard / Weber, Jeffrey S / Joshua, Anthony M / Hwu, Wen-Jen / Gangadhar, Tara C / Patnaik, Amita / Dronca, Roxana / Zarour, Hassane / Joseph, Richard W / Boasberg, Peter / Chmielowski, Bartosz / Mateus, Christine / Postow, Michael A / Gergich, Kevin / Elassaiss-Schaap, Jeroen / Li, Xiaoyun Nicole / Iannone, Robert / Ebbinghaus, Scot W / Kang, S Peter / Daud, Adil. ·Gustave Roussy and INSERM U981, Paris-Sud, France. Electronic address: caroline.robert@gustaveroussy.fr. · University of California Los Angeles, Los Angeles, CA, USA. · Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Angeles Clinic and Research Institute, Los Angeles, CA, USA. · Crown Princess Mary Cancer Centre, Westmead Hospital and Melanoma Institute Australia, Westmead, NSW, Australia; University of Sydney, Sydney, NSW, Australia. · H Lee Moffitt Cancer Center, Tampa, FL, USA. · Princess Margaret Cancer Centre, Toronto, ON, Canada. · University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA. · South Texas Accelerated Research Therapeutics, San Antonio, TX, USA. · Mayo Clinic, Rochester, MN, USA. · University of Pittsburgh, Pittsburgh, PA, USA. · Mayo Clinic, Jacksonville, FL, USA. · Gustave Roussy and INSERM U981, Paris-Sud, France. · Merck, Whitehouse Station, NJ, USA. · University of California San Francisco, San Francisco, CA, USA. ·Lancet · Pubmed #25034862.

ABSTRACT: BACKGROUND: The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma. METHODS: In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ≥18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. Primary endpoint was overall response rate (ORR) assessed with the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) by independent central review. Analysis was done on the full-analysis set (all treated patients with measurable disease at baseline). This study is registered with ClinicalTrials.gov, number NCT01295827. FINDINGS: 173 patients received pembrolizumab 2 mg/kg (n=89) or 10 mg/kg (n=84). Median follow-up duration was 8 months. ORR was 26% at both doses--21 of 81 patients in the 2 mg/kg group and 20 of 76 in the 10 mg/kg group (difference 0%, 95% CI -14 to 13; p=0·96). Treatment was well tolerated, with similar safety profiles in the 2 mg/kg and 10 mg/kg groups and no drug-related deaths. The most common drug-related adverse events of any grade in the 2 mg/kg and 10 mg/kg groups were fatigue (29 [33%] vs 31 [37%]), pruritus (23 [26%] vs 16 [19%]), and rash (16 [18%] vs 15 [18%]). Grade 3 fatigue, reported in five (3%) patients in the 2 mg/kg pembrolizumab group, was the only drug-related grade 3 to 4 adverse event reported in more than one patient. INTERPRETATION: The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options. FUNDING: Merck Sharp and Dohme.

6 Clinical Trial Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. 2013

Hamid, Omid / Robert, Caroline / Daud, Adil / Hodi, F Stephen / Hwu, Wen-Jen / Kefford, Richard / Wolchok, Jedd D / Hersey, Peter / Joseph, Richard W / Weber, Jeffrey S / Dronca, Roxana / Gangadhar, Tara C / Patnaik, Amita / Zarour, Hassane / Joshua, Anthony M / Gergich, Kevin / Elassaiss-Schaap, Jeroen / Algazi, Alain / Mateus, Christine / Boasberg, Peter / Tumeh, Paul C / Chmielowski, Bartosz / Ebbinghaus, Scot W / Li, Xiaoyun Nicole / Kang, S Peter / Ribas, Antoni. ·Angeles Clinic and Research Institute, Los Angeles, CA, USA. ·N Engl J Med · Pubmed #23724846.

ABSTRACT: BACKGROUND: The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. METHODS: We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. RESULTS: A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. CONCLUSIONS: In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. (Funded by Merck Sharp and Dohme; ClinicalTrials.gov number, NCT01295827.).

7 Article Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. 2019

Hamid, O / Robert, C / Daud, A / Hodi, F S / Hwu, W J / Kefford, R / Wolchok, J D / Hersey, P / Joseph, R / Weber, J S / Dronca, R / Mitchell, T C / Patnaik, A / Zarour, H M / Joshua, A M / Zhao, Q / Jensen, E / Ahsan, S / Ibrahim, N / Ribas, A. ·Medical Oncology, The Angeles Clinic and Research Institute, Los Angeles, USA. Electronic address: ohamid@theangelesclinic.org. · Department of Dermatology, Gustave Roussy, Villejuif; Department of Medicine, University of Paris-Sud, Paris, France. · Department of Medicine, University of California, San Francisco, San Francisco. · Medical Oncology, Dana-Farber Cancer Institute, Boston. · Department of Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. · Medical Oncology, Westmead Hospital, Westmead; Medical Oncology, Melanoma Institute Australia, Sydney; Medical Oncology, Macquarie University, Macquarie Park; Medical Oncology, University of Sydney, Sydney, Australia. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. · Medical Oncology, University of Sydney, Sydney, Australia; Department of Medicine, Centenary Institute, Sydney, Australia. · Medical Oncology, Mayo Clinic Cancer Center-Florida, Jacksonville. · Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, New York. · Division of Hematology Oncology, Abramson Cancer Center, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia. · Medical Oncology, South Texas Accelerated Research Therapeutics, San Antonio. · Department of Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, USA. · Medical Oncology, Melanoma Institute Australia, Sydney; Medical Oncology, University of Sydney, Sydney, Australia; Kinghorn Cancer Centre, St. Vincent's Hospital, Medical Oncology, Garvan Institute of Medical Research, Sydney; Medical Oncology, University of New South Wales, Sydney, Australia. · Merck & Co., Inc., Kenilworth. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA. ·Ann Oncol · Pubmed #30715153.

ABSTRACT: BACKGROUND: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. PATIENTS AND METHODS: Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). RESULTS: KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. CONCLUSIONS: This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT01295827.