A phase 3, international, multicenter, randomized, controlled trial of selective index lymph node resection versus therapeutic lymph node dissection after neoadjuvant immunotherapy for stage IIIB-D melanoma (MSLT-3/S2601/EORTC2519)
Abstract
TPS9609
Background:
Neoadjuvant immunotherapy (NAT) with immune checkpoint inhibitors (ICI) is a standard therapy for resectable stage III melanoma, with randomized trials demonstrating superior outcomes compared to adjuvant therapy alone. The phase 2 SWOG-1801 trial showed 72% EFS at 2 yrs for NAT & 49% for adjuvant PEMBRO (P=0.004), while the phase 3 NADINA trial confirmed superiority of NAT IPI/NIVO over adjuvant NIVO (2-year RFS 83.7% vs 57.2%, HR 0.32). Pathological response, particularly major pathological response (MPR; ≤10% viable tumor), strongly correlates with improved outcomes, with the International Neoadjuvant Melanoma Consortium (INMC) pooled analysis (N=610 ICI patients) demonstrating 3-yr RFS of 93% for MPR patients (pts) vs 41% for those with no pathological response. The PRADO trial demonstrated that selective index lymph node (ILN) resection (RES) can safely de-escalate surgery in MPR pts, with only 4/60 (6.7%) MPR pts recurring after median follow-up of 28.1 months, all locoregionally. ILN RES significantly reduced surgical morbidity & improved quality of life compared to therapeutic lymph node dissection (TLND). However, PRADO was a single-arm proof-of-concept study. An international survey of 117 melanoma experts showed 71% believe a phase 3 randomized controlled trial is needed to change practice. The MSLT-3 trial will definitively establish whether ILN RES is non-inferior to standard TLND for MPR pts.
Methods:
This phase 3, international,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 610 participants or records.
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