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Pembrolizumab for patients with PD-L1–positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx368

1569-8041

Janice M. Mehnert, Hope S. Rugo, Bert H. O’Neil, Armando Santoro, J. H. M. Schellens, Rachel Cohen, Toshihiko Doi, P.A. Ott, Michael J. Pishvaian, Igor Puzanov, Kyaw Aung, Chih‐Hung Hsu, Christophe Le Tourneau, J.C. Soria, Elena Élez, Kazuki Tamura, M. Gould, Guojun Zhao, Karen Stein, Sarina A. Piha‐Paul,

Lung Cancer Research Studies

Background: Among patients (pts) with advanced carcinoid/neuroendocrine tumors (NETs), expression of PD-L1 is associated with higher tumor grade. The multicohort phase 1b KEYNOTE-028 study (NCT02054806) evaluated safety and efficacy of pembrolizumab in pts with PD-L1–positive advanced solid tumors. This is the first report from the carcinoid and pancreatic NET (pNET) cohorts of this study. Methods: Eligibility criteria included: Carcinoid tumors or well- or moderately differentiated pNETs; PD-L1–positive (≥1% modified proportion score or interface pattern, QualTek IHC); failure of standard therapy; and ECOG PS ≤ 1. Pts received pembrolizumab 10 mg/kg Q2W for up to 2 y or until confirmed progression, intolerable toxicity, or consent withdrawal. Response was assessed every 8 wk for 6 mo then every 12 wk. The primary endpoint was ORR per RECIST v1.1 by investigator review. Results: 276 screened pts had tumor samples evaluable for PD-L1; 36% were positive. Among enrolled carcinoid (n = 25 [lung, n = 9; gut, n = 7; other, n = 9]) and pNET (n = 16) pts, respectively, median ages were 63 y and 61 y, 76% and 38% had ECOG PS of 1, and 44% and 50% had ≥2 prior therapies for metastatic disease. As of Jan 10, 2017, median (range) follow up was 18.9 (2.0–33.3) and 20.1 (4.5–30.4) mo. Treatment-related AEs (TRAEs) occurred in 17 (68%) carcinoid and 11 (69%) pNET pts; the most frequent (≥20%) were diarrhea (n = 7, 28%) and fatigue (n = 5, 20%) in carcinoid pts and fatigue (n = 6, 38%) and diarrhea (n = 4, 25%) in pNET pts. Grade ≥3 TRAEs occurred in 8 (32%) carcinoid pts (including diarrhea, n = 3; AST increased, n = 2; ALT increased; n = 2) and 0 pNET pts. One grade 4 AE (increased gamma-glutamyl transferase) and 1 death (unspecified cause) occurred in the carcinoid cohort; neither was treatment related. Three carcinoid pts (12%; 95% CI, 3%–31%) and 1 pNET pt (6%; 95% CI, 0%–30%) had objective responses; SD rates were 60% (n = 15) and 88% (n = 14). Durations of response were 6.9, 9.2, and 11.1 mo for the carcinoid responders; the pNET responder has an ongoing response of 17.6 mo. Conclusions: In pts with heavily pretreated carcinoid/pNET tumors, pembrolizumab was generally well tolerated and, in some pts, provided clinically meaningful antitumor activity. Clinical trial identification: ClinicalTrials.gov, NCT02054806; EudraCT Number, 2013-004507-39 Legal entity responsible for the study: Merck & Co., Inc., Kenilworth, NJ, USA Funding: This research was supported by Merck & Co., Inc., Kenilworth, NJ, USA Disclosure: H.S. Rugo: Research funding: Genentech/Roche, Novartis, Lilly, Eisai, Merck, Pfizer, OBI, Macrogenics, GTx pharma, Travel expenses, including accommodations: Mylan, Puma, B.H. O'Neil: Travel expenses, including accommodations: Amgen, A. Santoro: Advisory board member: Celgene, BMS, Takeda, vierBMS, MSD, Servier, Arqule, R.B. Cohen: Advisory Board member: Takeda, BMS, Zymeworks. Research funding: Merch, Cleave, Innate. Honoraria: Takeda, BMS, Zymeworks Travel expenses, including accommodations: Takeda, BMS, Zymeworks. T. Doi: Advisory Board, Research funding: Lilly, Chugai Pharma, Kyowa Hakko Kirin, Novartis, MSD, Daiichi Sankyo. Advisory Board: Amgen. Research funding: Taiho, Merk Serono, Astellas Pharma, Janssen, Boehringer-Ingelheim, Takeda, Pfizer, Sumitomo Group, Bayer, Celgene. P.A. Ott: Research funding: BMS, Merck, Neon Therapeutics, Armo BiosSciences, Celldex, MedImmune/AZ, Pfizer, CytomX. Honoraria: BMS, Merck, Neon Therapeutics, Celldex, Prizer, CytomX, Novartis, Alexion, Genentech/Roche. C. Le Tourneau: Advisory board member: MSD, BMS, AstraZeneca, Novartis. Honoraria: Merck Serono. Travel expenses, including accommodations: MSD, AstraZeneca, BMS. J-C. Soria: Honoraria: MSD. K. Tamura: Direct research support to the responsible project lead (e.g., Principal Investigator): Daiichi Sankyo, MSD, Pfizer, AstraZeneca. M. Gould, G. Zhao: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. K. Stein: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Stock ownership: Merck, Novartis, Sanofi, Pfizer. Travel expenses, including accommodations: Merck. All other authors have declared no conflicts of interest.