Zie ook dit artikel: https://kanker-actueel.nl/chirurgie-pdt-foto-dynamische-therapie-met-bremachlorin-geeft-veel-betere-overall-overleving-op-5-jaar-dan-alleen-chirurgie-van-melanomen-vanuit-moedervlekken-ontstaan.html

4 juni 2021: ASCO 2021

Uit een grote fase III studie (N = 1345) blijkt dat de werkzaamheid van pembrolizumab  (een vorm van immuuntherapie, ook wel anti-PD medicijnen of checkpointremmers genoemd) voor de behandeling van patiënten met geopereerde melanomen met een hoog risico (Stadium IIIB t/m stadium IV) beter was vergeleken met standaardbehandelingen van hoge dosis interferon (HDI) of ipilimumab.

De recidiefvrije overleving (RFS) was statistisch verbeterd in de pembrolizumab-groep (HR 0,740; 99,618% BI 0,571-0,958), terwijl de totale overleving niet statistisch was verbeterd maar met overlevingspercentages van 96 tot 98 procent voor de totale patiëntenpopulatie (HR 0,837; 96,3%) CI, 0,622-1,297) en de PD-L1+ patiëntenpopulatie (HR 0,883; 97,8% CI 0,604-1,291) op meting van 3,5 jaar natuurlijk wel goed te noemen.

Hoge dosis interferon en ipilimumab gaven wel meer graad 3 bijwerkingen (respectievelijk 69% en 43%) dan pembrolizumab (17%).

Deze studie werd gepresenteerd op ASCO 2021. Hier het abstract en hier het studieprotocol: NCT02506153.

Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma.

Authors:

Kenneth F. Grossmann, Megan Othus, Sapna Pradyuman Patel, Ahmad A. Tarhini, Vernon K. Sondak, Teresa M. Petrella, Thach-Giao Truong, Nikhil I. Khushalani, Justine Vanessa Cohen, Elizabeth Iannotti Buchbinder, Kari Lynn Kendra, Pauline Funchain, Karl D. Lewis, Bartosz Chmielowski, Hongli Li, James Moon, Krishna Soujanya Gunturu, Zeynep Eroglu, John M. Kirkwood, Antoni Ribas; Huntsman Cancer...

Research Funding:

U.S. National Institutes of Health, Pharmaceutical/Biotech Company

Background:

We assessed whether or not adjuvant pembrolizumab given over 1 year would improve OS and RFS in comparison to high dose ipilimumab (ipi10) or HDI - the two FDA-approved adjuvant treatments for high risk resected melanoma at the time of study design.Methods:Patients age 18 or greater with resected stages IIIA(N2), B, C and IV were eligible. Patients with CNS metastasis were excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel node positive disease. Prior therapy with PD-1 blockade, ipilimumab or interferon was not allowed. Two treatment arms were assigned based on stratification by stage, PD-L1 status (positive vs. negative vs. unknown), and intended control arm (HDI vs. Ipi10). Patients enrolled between 10/2015 and 8/2017 were randomized 1:1 to either the control arm [(1) interferon alfa-2b 20 MU/m2 IV days 1-5, weeks 1-4, followed by 10 MU/m2/d SC days 1, 3, and 5, weeks 5-52 (n=190), or (2) ipilimumab 10 mg/kg IV q3w for 4 doses, then q12w for up to 3 years (n=465)], or the experimental arm [pembrolizumab 200 mg IV q3w for 52 weeks (n=648)]. The study had three primary comparisons: 1) RFS among all patients, 2) OS among all patients, 3) OS among patients with PD-L1+ baseline biopsies.

Results: 1,426 patients were screened and 1,345 patients were randomized with 11%, 49%, 34%, and 6% AJCC7 stage IIIA(N2), IIIB, IIIC and IV, respectively. This final analysis was performed per-protocol 3.5 years from the date the last patient was randomized, with 512 RFS and 199 OS events. The pembrolizumab group had a statistically significant improvement in RFS compared to the control group (pooled HDI and ipi10) with HR 0.740 (99.618% CI, 0.571 to 0.958). There was no statistically signifcant improvement in OS in the 1,303 eligible randomized overall patient population with HR 0.837 (96.3% CI, 0.622 to 1.297), or among the 1,070 (82%) patients with PD-L1 positive baseline biopsies with HR 0.883 (97.8% CI, 0.604 to 1.291). Gr 3/4/5 event rates were as follows: HDI 69/9/0%, ipi10 43/5/0.5% and pembrolizumab 17/2/0.3%.

Conclusions:Pembrolizumab improves RFS but not OS compared to HDI or ipi10 in the adjuvant treatment of patients with high-risk resected melanoma. Pembrolizumab is a better tolerated adjuvant treatment regimen than HDI or Ipi10. Support: NIH/NCI NCTN grants CA180888, CA180819, CA180820, CA180863; and in part by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial Acknowledgement: With special thanks to Elad Sharon, MD, MPH, and Larissa Korde, MD, MPH. National Cancer Institute, Investigational Drug Branch, for their contributions to this trial, as well as Nageatte Ibrahim, MD, and Sama Ahsan, MD Merck. Clinical trial information: NCT02506153


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