145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)

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.