Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial.
Mary L. Disis,Mary L. Disis,Matthew H. Taylor,Karen Kelly,J. Thaddeus Beck,Michael S. Gordon,Kathleen M. Moore,Manish R. Patel,Jorge Chaves,Haeseong Park,Alain C. Mita,Erika Hamilton,Christina M. Annunziata,Hans Juergen Grote,Anja von Heydebreck,Jaspreet Grewal,Jaspreet Grewal,Vikram Chand,Vikram Chand,James L. Gulley +19 more
TLDR
Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer in an expansion cohort of a phase 1b, open-label study.Abstract:
Importance Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. Objective To assess the efficacy and safety of avelumab, an anti–programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. Design, Setting, and Participants In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. Intervention Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression–based analyses, and safety. Results A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. Conclusions and Relevance Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer. Trial Registration ClinicalTrials.gov identifier:NCT01772004read more
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RAS-targeted therapies: is the undruggable drugged?
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Dmitriy Zamarin,Robert A. Burger,Michael W. Sill,Daniel J. Powell,Heather A. Lankes,Michael Feldman,Oliver Zivanovic,Camille C. Gunderson,Emily M. Ko,Cara Mathews,Sudarshan K. Sharma,Andrea R. Hagemann,Samir N. Khleif,Carol Aghajanian +13 more
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Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer.
Anniina Färkkilä,Doga Gulhan,Julia Casado,Connor A. Jacobson,Huy V. Nguyen,Bose Kochupurakkal,Zoltan Maliga,Clarence Yapp,Yu-An Chen,Denis Schapiro,Yinghui Zhou,Julie R. Graham,Bruce J. Dezube,Pamela N. Munster,Sandro Santagata,Elizabeth P. Garcia,Scott J. Rodig,Ana Lako,Dipanjan Chowdhury,Geoffrey I. Shapiro,Ursula A. Matulonis,Peter J. Park,Sampsa Hautaniemi,Peter K. Sorger,Elizabeth M. Swisher,Alan D. D'Andrea,Panagiotis A. Konstantinopoulos +26 more
TL;DR: An integrated genomic and immunomics analysis of tumor samples from the same patients is performed to find potential predictive biomarkers of response to such combination therapy.
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Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial
Joyce F. Liu,Christina I. Herold,Kathryn P. Gray,Richard T. Penson,Neil S. Horowitz,Panagiotis A. Konstantinopoulos,Cesar M. Castro,Sarah J. Hill,Jennifer Curtis,Weixiu Luo,Ursula A. Matulonis,Stephen A. Cannistra,Don S. Dizon,Don S. Dizon +13 more
TL;DR: The nivolumab with bevacizumab combination appeared to show activity in patients with relapsed ovarian cancer, with greater activity in the platinum-sensitive setting, and alternative combinational strategies may be necessary in theatinum-resistant setting.
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Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer.
Panagiotis A. Konstantinopoulos,Weixiu Luo,Joyce F. Liu,Doga Gulhan,Carolyn N. Krasner,Jeffrey J. Ishizuka,Allison Gockley,Mary K. Buss,Whitfield B. Growdon,Heather Crowe,Susana M. Campos,Neal I. Lindeman,Sarah J. Hill,Elizabeth H. Stover,Susan Schumer,Alexi A. Wright,Jennifer Curtis,Roxanne Quinn,Christin Whalen,Kathryn P. Gray,Richard T. Penson,Stephen A. Cannistra,Gini F. Fleming,Ursula A. Matulonis +23 more
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References
More filters
Journal ArticleDOI
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Jacques Ferlay,Isabelle Soerjomataram,Rajesh Dikshit,Sultan Eser,Colin Mathers,Marise Souto Rebelo,Donald Maxwell Parkin,David Forman,Freddie Bray +8 more
TL;DR: The GLOBOCAN series of the International Agency for Research on Cancer (IARC) as mentioned in this paper provides estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012.
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Journal ArticleDOI
Cancer statistics, 2017
TL;DR: The American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival.
Book ChapterDOI
World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects
TL;DR: Comparing the socialist nature of many European counties, there is a requirement that provision be made for patients to be made whole regardless of the outcomes of the trial or if they happened to have been randomized to a control group that did not enjoy the benefits of a successful experimental intervention.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
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