KEY TAKEAWAYS
- The LEAP-001 phase 3 trial aimed to assess the efficacy and safety of LEN/PEMBRO vs paclitaxel + carboplatin AUC regimens in pts with EC.
- The primary endpoints were PFS and OS.
- The results revealed that the OS and PFS goals were not met in pMMR advanced/recurrent EC; safety profiles were consistent & manageable.
This trial evaluated first-line treatment with Lenvatinib + pembrolizumab (LEN/PEMBRO) versus chemotherapy (chemo) in patients with advanced or recurrent endometrial cancer(EC), following neo/adjuvant settings or any prior systemic therapy including neo/adjuvant settings.
Sandro Pignata and the team investigated the comparative efficacy of LEN/PEMBRO vs paclitaxel + carboplatin in pts with advanced/recurrent EC.
Researchers enrolled pts with stage III–IV or recurrent EC with visible radiographic evidence, without prior chemo or disease progression ≥6 months after neo/adjuvant platinum-based therapy.
They randomized the pts in a ratio 1:1 by stratifying based on mismatch repair status (pMMR/dMMR) and ECOG performance status (0/1), presence of measurable disease, and prior chemo/chemoradiation.
Treatments were LEN/PEMBRO (20 mg daily, 200 mg every 3 weeks respectively) vs paclitaxel + carboplatin (175 mg/m2 every 3 weeks 6 every 3 weeks respectively). The primary endpoints were progression-free survival (PFS) and overall survival (OS) in proficient mismatch repair status (pMMR) and overall populations. Secondary endpoints included objective response rate (ORR), safety, and exploratory analysis of response duration and tumor histology outcomes.
The results indicated that the final analysis as of October 2, 2023, had a median follow-up of 38.4 months (range, 30.3–52.9), the LEN/PEMBRO regimen did not achieve a statistically significant level for non-inferiority in OS compared to chemo in the pMMR population (HR, 1.02 [95% CI, 0.83–1.26]; non-inferiority P = 0.2459875).
PFS and OS outcomes corresponding to LEN/PEMBRO vs chemo by histological subtype will be presented for both the pMMR population and all patients. Treatment-related adverse events occurred in 97.9% (411 of 420) of patients in the LEN/PEMBRO group compared to 96.8% (398 of 411) in the chemo group.
In the pMMR subgroup, the study compared LEN/PEMBRO and chemo for advanced or recurrent EC. LEN/PEMBRO demonstrated an ORR of 50.6% (95% CI, 45.0–56.2), while chemo had an ORR of 54.7% (95% CI, 49.0–60.2). Among all pts, ORRs were 55.7% (95% CI, 50.8–60.5) for LEN/PEMBRO and 55.5% (95% CI, 50.6–60.3) for chemotherapy.
Median duration of response (DOR) favored LEN/PEMBRO with 16.1 months (range, 1.0+ to 48.7+) in the pMMR subgroup and 23.2 months (range, 1.0+ to 49.0+) in all-comers, compared to 10.6 months (range, 1.1+ to 43.8+) and 10.9 months (range, 1.1+ to 46.9+) respectively for chemo.
Over the aspect of OS in the pMMR subgroup, the study did not find statistically significant differences between LEN/PEMBRO and chemo, with a one-sided non-inferiority P-value of 0.2459875 showing nonsignificance. Therefore, no further statistical testing of efficacy endpoints was conducted per the prespecified multiplicity strategy for type 1 error control.
These results highlighted similar efficacy and safety profiles for both treatment regimens in these pts, despite longer response durations observed with LEN/PEMBRO.
The study concluded that statistical goals for OS and PFS in pMMR advanced/recurrent EC were not achieved. In further sub-analyses for identification of the prospective subgroup that will receive benefits from LEN/PEMBRO will be presented. Consistent and manageable safety profiles were observed.
The trial was sponsored by Merck Sharp & Dohme LLC.
Source: https://cslide.ctimeetingtech.com/gynae24hybrid/attendee/confcal/show/session/10
Clinical Trial: https://www.clinicaltrials.gov/study/NCT03884101
Pignata S, Marth c, Moore R G, (2024). “Phase III ENGOT-En9/LEAP-001 study: Lenvatinib + pembrolizumab (LEN/PEMBRO) vs chemotherapy (chemo) as first-line (1L) therapy for advanced or recurrent endometrial cancer.” Presented at ESMO-GC 2024. (Abstract 39MO)
