Aims
As part of a phase 1b/2 study (NCT02501096), patients with previously treated, advanced EC that was not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) (n=94), treated with LEN (20 mg orally once daily) + PEMBRO (200 mg IV Q3W), had an objective response rate (ORR) of 38.3% (95% CI: 28.5-48.9) (by independent imaging review [IIR] per RECIST v1.1). In this post hoc analysis, we assessed subgroups from this population who received LEN + PEMBRO in an early-treatment setting.
Methods
Two subgroups were examined: (S1) 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); (S2) patients from S1 with local-regional disease at diagnosis who had received only adjuvant cytotoxic therapy. Neither subgroup had restrictions on prior hormonal or chemoradiation therapies. Tumor responses were assessed by IIR per RECIST v1.1.
Results
S1 included 63 patients; S2 had 21 patients. ORR (95% CI) was 41.3% (29.0-54.4) for S1 and 57.1% (34.0-78.2) for S2. Median duration of response was not estimable in either subgroup. In S1, median PFS (95% CI) was 7.5 months (4.4-8.9) and 8.3 months (4.4-not estimable) in S2. Median OS was 18.3 months (95% CI: 15.0–not estimable) in S1 and not estimable in S2. In S1, treatment-related adverse events (TRAEs) occurred in 98% patients (67% ≥grade 3); 19% patients discontinued 1 or both drugs due to a TRAE. Serious TRAEs occurred in 29% patients; and 3% patients died from a TRAE. Safety for S2 was generally similar to S1 profile.
Conclusions
The efficacy of LEN + PEMBRO for early-line treatment of advanced non MSI-H or dMMR EC appears promising. No new safety signals emerged. A phase 3 study of LEN + PEMBRO for first-line treatment in advanced/recurrent EC is underway (NCT03884101).