Sie sind bereits registriert?
Loggen Sie sich mit Ihrem Universimed-Benutzerkonto ein:
Sie sind noch nicht registriert?
Registrieren Sie sich jetzt kostenlos auf universimed.com und erhalten Sie Zugang zu allen Artikeln, bewerten Sie Inhalte und speichern Sie interessante Beiträge in Ihrem persönlichen Bereich
zum späteren Lesen. Ihre Registrierung ist für alle Unversimed-Portale gültig. (inkl. allgemeineplus.at & med-Diplom.at)
First-Line Immune Checkpoint Inhibitor Therapy for MSI-High Metastatic Colon Cancer
Pembrolizumab achieves superior response, progression-free survival (PFS) and overall survival compared with first-line chemotherapy in patients with microsatellite-instability (MSI)–high metastatic colorectal cancer (CRC). Nonrandomized trials have also indicated a high degree of effectiveness for single-agent nivolumab or the combination of ipilimumab and nivolumab (ipi/nivo).
Investigators now report results of the industry-sponsored, phase 3 Checkmate 8HW trial comparing treatment with first-line chemotherapy versus ipi/nivo in patients with previously untreated unresectable or metastatic MSI-high CRC. Patients were randomly assigned to treatment with investigators' choice of chemotherapy with or without a targeted agent, or nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks for 12 weeks, followed by nivolumab maintenance (480 mg) every 4 weeks. Of 303 patients, 68% had right-sided primaries, 39% had liver and 42% had peritoneal metastases, 84% had centrally confirmed MSI-high status, and 13% had known Lynch syndrome.
At a median follow-up of 31.5 months, the primary endpoint of PFS in the patients with centrally confirmed MSI-high status was superior for ipi/nivo compared with chemotherapy (P<0.001), both at 12 months (79% vs. 21%) and 24 months (72% vs. 14%). Estimated mean survival time at 24 months was numerically superior for ipi/nivo compared with chemotherapy (19.2 vs. 8.6 months). All subgroups, including patients with RAS and BRAF mutations, achieved superior PFS with ipi/nivo. Treatment-related grade 3/4 serious adverse events were less common with ipi/nivo than chemotherapy (23% vs. 49%). No new safety signals were observed.
Comment
Ipi/nivo was superior to chemotherapy as first-line treatment in MSI-high metastatic CRC, with a remarkably high PFS rate of 72% at 2 years into treatment. Results from a third treatment arm of the trial comparing single-agent nivolumab to ipi/nivo are pending and will address whether ipi/nivo is superior to nivolumab alone. Ipi/nivo joins pembrolizumab as a standard of care for MSI-high metastatic CRC.
Citation(s)
Author:
Andre T et al.
Title:
Nivolumab plus ipilimumab in microsatellite-instability–high metastatic colorectal cancer.
Source:
N Engl J Med
2024
Nov
28; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
David H. Ilson, MD, PhD