Pembrolizumab versus Ipilimumab in Advanced Melanoma
Caroline Robert,Caroline Robert,Caroline Robert,Jacob Schachter,Georgina V. Long,Ana Arance,Jean-Jacques Grob,Laurent Mortier,Laurent Mortier,Adil Daud,Matteo S. Carlino,Catriona M. McNeil,Michal Lotem,James Larkin,Paul Lorigan,Bart Neyns,Christian U. Blank,Omid Hamid,Christine Mateus,Christine Mateus,Ronnie Shapira-Frommer,Ronnie Shapira-Frommer,Michele Kosh,Honghong Zhou,Nageatte Ibrahim,Scot Ebbinghaus,Antoni Ribas +26 more
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The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.Abstract:
Background The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Methods In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progressionfree and overall survival. Results The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P = 0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P = 0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%). Conclusions The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials .gov number, NCT01866319.)read more
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Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.
Vicky Makker,Drew W. Rasco,Nicholas J. Vogelzang,Marcia S. Brose,Allen Lee Cohn,James W. Mier,Christopher Di Simone,David M. Hyman,Daniel E. Stepan,Corina E. Dutcus,Emmett V. Schmidt,Matthew Guo,Pallavi Sachdev,Robert Shumaker,Carol Aghajanian,Matthew H. Taylor +15 more
TL;DR: Lenvatinib plus pembrolizumab showed anti-tumour activity in patients with advanced recurrent endometrial cancer with a safety profile that was similar to those previously reported for lenvatinIB and pembrology monotherapies, apart from an increased frequency of hypothyroidism.
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Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients
Guillermo de Velasco,Youjin Je,Dominick Bossé,Mark M. Awad,Patrick A. Ott,Raphael Brandao Moreira,Fabio A.B. Schutz,Joaquim Bellmunt,Guru Sonpavde,F. Stephen Hodi,Toni K. Choueiri +10 more
TL;DR: There is substantial evidence that ICIs are associated with a small but significant increase in risk of selected all-grade irAEs and high-grade gastrointestinal and liver toxicities, and AEs should be recognized promptly as early interventions may alleviate future complications.
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The gut microbiota influences anticancer immunosurveillance and general health.
Bertrand Routy,Vancheswaran Gopalakrishnan,Romain Daillère,Laurence Zitvogel,Jennifer A. Wargo,Guido Kroemer +5 more
TL;DR: Key contributors to this field of research discuss connections between gut bacteria, anticancer immunity, and general health, with a focus on specific bacterial species consistently associated with favourable clinical outcomes of anticancer immunotherapy, and explore the potential mechanisms.
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Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC
Paul C. Tumeh,Matthew D. Hellmann,Omid Hamid,Katy K. Tsai,Kimberly Loo,Matthew A. Gubens,Michael Rosenblum,Christina L. Harview,Janis M. Taube,Nathan Handley,Neharika Khurana,Adi Nosrati,Matthew F. Krummel,Andrew Tucker,Eduardo V. Sosa,Phillip J. Sanchez,Nooriel Banayan,Juan C. Osorio,Dan L. Nguyen-Kim,Jeremy Chang,I. Peter Shintaku,Peter D. Boasberg,Emma Taylor,Pamela N. Munster,Alain Algazi,Bartosz Chmielowski,Reinhard Dummer,Tristan Grogan,David Elashoff,Jimmy Hwang,Simone M. Goldinger,Edward B. Garon,Robert H. Pierce,Adil Daud +33 more
TL;DR: Liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases wereassociated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome.
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Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer
Vicky Makker,Matthew H. Taylor,Carol Aghajanian,Ana Oaknin,James W. Mier,Allen Lee Cohn,Margarita Romeo,Raquel Bratos,Marcia S. Brose,Christopher DiSimone,Mark Messing,Daniel E. Stepan,Corina E. Dutcus,Jane Wu,Emmett V. Schmidt,Robert Orlowski,Pallavi Sachdev,Robert Shumaker,Antonio Casado Herraez +18 more
TL;DR: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status.
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TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
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