As part of an ongoing phase Ib/II study ( NCT02501096 ) in patients with selected solid tumors, Lenvatinib [ Lenvima ] ( 20 mg PO [ per os ] QD [ once a day ] ) + Pembrolizumab [ Keytruda ] ( 200 mg IV Q3W [ every 3 weeks ] ) displayed substantial and durable antitumor activity in advanced endometrial cancer.
In previously treated endometrial cancer that was not microsatellite instability high ( MSI-H ) or mismatch repair deficient ( dMMR; n=94 patients ), the objective response rate ( ORR ) by independent imaging review ( IIR ) per RECIST 1.1 was 38.3% ( 95% CI 28.5–48.9 ).
In this post hoc analysis, researchers have assessed 2 subgroups of patients with previously treated, advanced, non MSI-H or dMMR EC who received Lenvatinib + Pembrolizumab in an early-treatment setting.
Patients were examined in 2 subgroups: (1) patients with only 1 prior line of cytotoxic therapy regardless of surgical stage or setting ( adjuvant treatment for local-regional disease or treatment for metastatic disease ); and (2) patients from subgroup 1 with local-regional disease at diagnosis who have received only adjuvant cytotoxic therapy.
There were no restrictions on prior hormonal or chemoradiation therapies in either subgroup.
Tumor responses were assessed by IIR per RECIST 1.1.
Subgroup 1 included 63 patients and subgroup 2 had 21 patients.
ORR ( 95% CI ) was 41.3% ( 29.0–54.4 ) for subgroup 1 and 57.1% ( 34.0–78.2 ) for subgroup 2. Additional efficacy outcomes were: complete response 8 ( 12.7% ) and 5 ( 23.8% ); partial response: 18 ( 28.6% ) and 7 ( 33.3% ); median progression-free survival, months ( 95% CI ) 7.5 ( 4.4–8.9 ) and 8.3 ( 4.4–NE [ not-estimated ] ); median overall survival, months ( 95% CI ) 18.3 ( 15.0–NE ) and NE ( 13.2–NE ), respectively.
In subgroup 1, treatment-related adverse events ( TRAEs ) occurred in 62 ( 98% ) patients ( 42 [ 67% ] grade 3 or more ).
TRAEs led to study-drug interruption of one or both drugs in 43 ( 68% ) patients and dose reductions of Lenvatinib in 42 ( 67% ) patients; 12 ( 19% ) patients discontinued one or both drugs due to a TRAE.
Serious TRAEs occurred in 18 ( 29% ) patients and 2 ( 3% ) patients died from a TRAE.
The safety profile for subgroup 2 was generally similar to the profile for subgroup 1.
In conclusion, the efficacy of Lenvatinib + Pembrolizumab for early-line treatment of advanced non MSI-H or dMMR endometrial cancer appears promising.
No new safety signals have emerged. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020