21 september 2023: Zie ook dit artikel: https://kanker-actueel.nl/maretakinjecties-hoge-dosis-doen-kanker-volledig-verdwijnen-bij-vrouw-met-recidief-van-merkelcel-carcinoom-75-jaar-en-bij-vrouw-met-borstkanker-in-beide-borsten-50-jaar-zonder-andere-behandelingen-beide-vrouwen-leven-al-jaren-zonder-kanker.html

21 september 2023: Bron: The Lancet, Published:July 11, 2023

Uit een fase II studie ADMEC-O uitgevoerd in 20 verschillende ziekenhuizen in Duitsland en Nederland bij totaal 179 patiënten die volledig waren geopereerd aan een Merkelcelcarcinoom blijkt immuuntherapie met de anti-PD remmer Nivolumab de ziektevrije overleving met 11 procent te verbeteren (84 vs 73 procent) in vergelijking met de observatiegroep. 

Patiënten uit de observatiegroep hadden eerder en meer radiotherapie - bestraling nodig dan de groep die Nivolumab kreeg. Hoewel dit nog een tussenevaluatie is van de 4-jarige studie is er nog geen statistische significantie bereikt. Maar de resultaten waren zo veelbelovend en goed dat deze tussenevaluatie nu al werd gepubliceerd in The Lancet

Uit het abstract:

  • Het 1-jaars ziektevrije overlevingspercentage (DFS) voor de nivolumabgroep was 85%, en het 2-jaars DFS-percentage was 84%.
  • In de observatiegroep was het 1-jarige DFS-percentage 77% (95%-BI: 64-86) en het 2-jarige DFS-percentage 73%.
  • Behandeling met nivolumab als adjuvante therapie resulteerde in een absolute risicoreductie van 0,091 bij 1-jarige ziektevrije overleving en 0,10 bij 2-jarige ziektevrije overleving, vergeleken met alleen observatie.
  • Bijwerkingen van graad 3 tot 4 traden op bij 42% van de patiënten behandeld met nivolumab en bij 11% van de patiënten in de observatiegroep.
  • Er zijn geen behandelingsgerelateerde sterfgevallen gemeld.
Zie ook dit studierapport waarvan abstract verderop in artikel Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time From Diagnosis

Het volledige studierapport van studie met Nivolumab is tegen betaling in te zien. Hier het abstract van de studie:

Adjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial

Published:July 11, 2023DOI:https://doi.org/10.1016/S0140-6736(23)00769-9

Summary

Background

Merkel cell carcinoma (MCC) is an immunogenic but aggressive skin cancer. Even after complete resection and radiation, relapse rates are high. PD-1 and PD-L1 checkpoint inhibitors showed clinical benefit in advanced MCC. We aimed to assess efficacy and safety of adjuvant immune checkpoint inhibition in completely resected MCC (ie, a setting without an established systemic standard-of-care treatment).

Methods

In this multicentre phase 2 trial, patients (any stage, Eastern Cooperative Oncology Group performance status 0–1) at 20 academic medical centres in Germany and the Netherlands with completely resected MCC lesions were randomly assigned 2:1 to receive nivolumab 480 mg every 4 weeks for 1 year, or observation, stratified by stage (American Joint Committee on Cancer stages 1–2 vs stages 3–4), age (<65 vs ≥65 years), and sex. Landmark disease-free survival (DFS) at 12 and 24 months was the primary endpoint, assessed in the intention-to-treat populations. Overall survival and safety were secondary endpoints. This planned interim analysis was triggered when the last-patient-in was followed up for more than 1 year. This study is registered with ClinicalTrials.gov (NCT02196961) and with the EU Clinical Trials Register (2013-000043-78).

Findings

Between Oct 1, 2014, and Aug 31, 2020, 179 patients were enrolled (116 [65%] stage 3–4, 122 [68%] ≥65 years, 111 [62%] male). Stratification factors (stage, age, sex) were balanced across the nivolumab (n=118) and internal control group (observation, n=61); adjuvant radiotherapy was more common in the control group. At a median follow-up of 24·3 months (IQR 19·2–33·4), median DFS was not reached (between-groups hazard ratio 0·58, 95% CI 0·30–1·12); DFS rates in the nivolumab group were 85% at 12 months and 84% at 24 months, and in the observation group were 77% at 12 months and 73% at 24 months. Overall survival results were not yet mature. Grade 3–4 adverse events occurred in 48 [42%] of 115 patients who received at least one dose of nivolumab and seven [11%] of 61 patients in the observation group. No treatment-related deaths were reported.

Interpretation

Adjuvant therapy with nivolumab resulted in an absolute risk reduction of 9% (1-year DFS) and 10% (2-year DFS). The present interim analysis of ADMEC-O might suggest clinical use of nivolumab in this area of unmet medical need. However, overall survival events rates, with ten events in the active treatment group and six events in the half-the-size observation group, are not mature enough to draw conclusions. The explorative data of our trial support the continuation of ongoing, randomised trials in this area. ADMEC-O suggests that adjuvant immunotherapy is clinically feasible in this area of unmet medical need.

Funding

Bristol Myers Squibb.

Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time From Diagnosis

Aubriana M. McEvoy, MD, MS1,2; Kristina Lachance, MS1; Daniel S. Hippe, MS1,3; et alKelsey Cahill, BS1; Yasman Moshiri, MD1; Christopher W. Lewis, MD1,4; Neha Singh, BS1; Song Y. Park, MD1; Zoe Thuesmunn, BS1; Maclean M. Cook, BS1; Nora A. Alexander, BS1; Lauren Zawacki, BS1; Hannah Thomas, BS1; Kelly G. Paulson, MD, PhD1,5; Paul Nghiem, MD, PhD1,3
Author Affiliations Article Information
JAMA Dermatol. 2022;158(4):382-389. doi:10.1001/jamadermatol.2021.6096
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Key Points

Question  What is the risk that Merkel cell carcinoma (MCC) will recur based on a patient’s cancer stage and time since diagnosis?

Findings  In this cohort study of 618 patients from a large data repository, 40% of whom experienced a recurrence, stage was a powerful prognostic factor: at 5 years, 80% of patients with pathologic stage I were without MCC recurrence vs 28% of patients with stage IV. Approximately 95% of all MCC recurrences arose within 3 years of diagnosis.

Meaning  Recurrence data can help clinicians determine which patients with MCC merit intensive surveillance and when de-escalation of surveillance is appropriate.

Abstract

Importance  Merkel cell carcinoma (MCC) often behaves aggressively; however, disease-recurrence data are not captured in national databases, and it is unclear what proportion of patients with MCC experience a recurrence (estimates vary from 27%-77%). Stage-specific recurrence data that includes time from diagnosis would provide more precise prognostic information and contribute to risk-appropriate clinical surveillance.

Objective  To estimate risk of stage-specific MCC recurrence and mortality over time since diagnosis.

Design, Setting, and Participants  This prospective cohort study included 618 patients with MCC who were prospectively enrolled in a Seattle-based data repository between 2003 and 2019. Of these patients, 223 experienced a recurrence of MCC. Data analysis was performed July 2019 to November 2021.

Main Outcomes and Measures  Stage-specific recurrence and survival, as well as cumulative incidence and Kaplan-Meier analyses.

Results  Among the 618 patients included in the analysis (median age, 69 [11-98] years; 227 [37%] female), the 5-year recurrence rate for MCC was 40%. Risk of recurrence in the first year was high (11% for patients with pathologic stage I, 33% for pathologic stage IIA/IIB, 30% for pathologic stage IIIA, 45% for pathologic stage IIIB, and 58% for pathologic stage IV), with 95% of recurrences occurring within the first 3 years. Median follow-up among living patients was 4.3 years. Beyond stage, 4 factors were associated with increased recurrence risk in univariable analyses: immunosuppression (hazard ratio , 2.4; 95% CI, 1.7-3.3; P < .001), male sex (HR, 1.9; 95% CI, 1.4-2.5; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; 95% CI, 1.4-4.0; P = .001), and older age (HR, 1.1; 95% CI, 1.0-1.3; P = .06 for each 10-year increase). Among 187 deaths in the cohort, 121 (65%) were due to MCC. The MCC-specific survival rate was strongly stage dependent (95% at 5 years for patients with pathologic stage I vs 41% for pathologic stage IV). Among patients presenting with stage I to II MCC, a local recurrence (17 arising within/adjacent to the primary tumor scar) did not appreciably diminish survival compared with patients who had no recurrence (85% vs 88% MCC-specific survival at 5 years).

Conclusions and Relevance  In this cohort study, the MCC recurrence rate (approximately 40%) was notably different than that reported for invasive melanoma (approximately 19%), squamous cell carcinoma (approximately 5%-9%), or basal cell carcinoma (approximately 1%-2%) following definitive therapy. Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest.



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Article info

Publication history

Published: July 11, 2023

Identification

DOI: https://doi.org/10.1016/S0140-6736(23)00769-9

Copyright

© 2023 Elsevier Ltd. All rights reserved.

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immuuntherapie, nivolumab, merkelcelcarcinoom, huidkanker, ziektevrije overleving


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