Princess Máxima Center, Utrecht, Netherlands
Alexander M. Eggermont , Christian U. Blank , Mario Mandalà , Georgina V. Long , Victoria Atkinson , Stéphane Dalle , Andrew Mark Haydon , Andrey Meshcheryakov , Muhammad Khattak , Matteo S. Carlino , Shahneen Kaur Sandhu , Susana Puig , Paolo Antonio Ascierto , Alexander Christopher Jonathan Van Akkooi , Clemens Krepler , Nageatte Ibrahim , Sandrine Marreaud , Michal Kicinski , Stefan Suciu , Caroline Robert
Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594
N pts | 3-yr RFS rate | Stratified by stage at randomization | |||
---|---|---|---|---|---|
Pembrolizumab | Placebo | HR | CI (HR)* | ||
Overall population | 1019 | 64% | 44% | 0.56 | 0.47-0.68 |
PD-L1 positive | 853 | 65% | 46% | 0.57 | 0.43-0.74 |
PD-L1 negative | 116 | 57% | 33% | 0.45 | 0.23-0.90 |
Stage IIIA | 152 | 81% | 66% | 0.50 | 0.22-1.16 |
Stage IIIB | 472 | 66% | 47% | 0.56 | 0.39-0.81 |
Stage IIIC | 395 | 54% | 32% | 0.57 | 0.40-0.81 |
BRAF-mutated | 440 | 62% | 37% | 0.51 | 0.36-0.73 |
BRAF-WT | 448 | 62% | 47% | 0.66 | 0.46-0.95 |
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Abstract Disclosures
2021 ASCO Annual Meeting
First Author: Alexander M. Eggermont
2023 ASCO Annual Meeting
First Author: Heather A. Wakelee
2022 ASCO Genitourinary Cancers Symposium
First Author: Yohann Loriot
2023 ASCO Annual Meeting
First Author: Jason J. Luke