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145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)
  1. N Colombo,
  2. D Lorusso3,
  3. AD Santin4,
  4. YM Kim5,
  5. AC Herráez6,
  6. K Yonemori7,
  7. K Fujiwara8,
  8. E Colomba9,
  9. DS Miller10,
  10. S Pignata11,
  11. BJ Monk12,
  12. EM Guerra13,
  13. R Kristeleit14,
  14. M Orlando15,
  15. UA Sanli16,
  16. L Dutta17,
  17. R Orlowski18,
  18. M Ren17 and
  19. V Makker19
  1. 1Gynecologic Oncology Program, University of Milan-Bicocca, European Institute of Oncology IRCCS, Milan, Italy
  2. 2Gynecologic Oncology Program, University of Milan-Bicocca, European Institute of Oncology IRCCS, Milan, Italy
  3. 3Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
  4. 4Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA
  5. 5Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Korea, Rep. of South
  6. 6Department of Medical Oncology, San Carlos University Teaching Hospital, Madrid, Spain
  7. 7Department of Breast and Medical Oncology, National Cancer Center Hospital: Kokuritsu Gan Kenkyu Center Chuo Byoin, Tokyo, Japan
  8. 8Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan
  9. 9Department of Cancer Medicine, Gustave Roussy Cancerology Institute, Villejuif, GINECO group, France
  10. 10Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, Dallas, USA
  11. 11Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, Naples, Italy
  12. 12Arizona Oncology (US Oncology Network), University of Arizona, Creighton University, Phoenix, USA
  13. 13Servicio de Oncología Médica, Hospital Universitario Ramón y Cajal, Madrid, Spain
  14. 14Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  15. 15Oncologia Clinica, Instituto Alexander Fleming, Buenos Aires, Argentina
  16. 16Department of Medical Oncology, Ege University, Izmir, Turkey
  17. 17Clinical Research, Eisai Inc., Woodcliff Lake, USA
  18. 18Late Stage Clinical Development, Merck and Co., Inc., Kenilworth, USA
  19. 19Department of Medicine, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical Center, New York, USA


Introduction/Background*In Study 309/KEYNOTE-775, lenvatinib+pembrolizumab showed significant and clinically meaningful improvements in OS, PFS, and ORR versus treatment of physician’s choice (TPC) in aEC patients following prior platinum-based therapy. Safety considerations are also important in EC. Herein, we characterize common adverse reactions (ARs) in patients with aEC in Study 309/KEYNOTE-775 and their respective management strategies. Additionally, the clinician’s role in proactively managing ARs will be highlighted.

Methodology In Study 309/KEYNOTE-775, patients were randomized to lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 weeks on/1 week off). Herein, characterization of key ARs is based on incidence and known association with lenvatinib+pembrolizumab, and interventions for ARs in aEC patients. Key ARs are grouped by preferred terms per FDA definitions for ARs in patients with endometrial carcinoma from the US prescribing information; ARs include hypertension, musculoskeletal pain, fatigue, nausea, diarrhea, decreased appetite, stomatitis, vomiting, hypothyroidism, palmar-plantar erythrodysesthesia (PPES), and decreased weight.

Result(s)*Median times (weeks) to first onset of key ARs [any grade] were: hypertension (2.1), fatigue (2.3), musculoskeletal pain (3.2), nausea (4.7), decreased appetite (4.9), stomatitis (4.9), vomiting (7.6), diarrhea (7.9), hypothyroidism (8.9), PPES (9.6), and decreased weight (10.7). Among ARs described, those that led to withdrawal of lenvatinib included decreased appetite (2%), fatigue (2%), hypertension (2%), diarrhea (1%), musculoskeletal pain (1%), vomiting (1%), and decreased weight (1%); only decreased appetite (1%) and diarrhea (1%) led to withdrawal of pembrolizumab. Hypertension most frequently led to lenvatinib dose reduction (18%); diarrhea and hypertension most frequently led to dose interruption of lenvatinib (11% each) as last action taken with lenvatinib. Diarrhea most frequently led to pembrolizumab interruption (8%). Change in sum of target lesion diameters over time, exposure-adjusted ARs, and AR management strategies will be reported.

Conclusion*In general, ARs due to lenvatinib+pembrolizumab were as expected and often occurred within 3 months of treatment initiation. As will be presented, clinicians play a critical role in prompt identification and AR-directed management of patients with aEC; such management may potentially reduce treatment interruption(s) and/or lenvatinib dose reduction.

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