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25 februari 2022: Bron: Annals of Oncology Published:February 02, 2022

Uit de fase III CheckMate 743-studie blijkt dat immuuntherapie als eerstelijns met de combinatie van ipilimumab plus nivolumab betere overall overleving geeft in vergelijking met chemotherapie met platina plus pemetrexed bij patiënten met inoperabele kwaadaardige asbestkanker - longmesothelioom . De combinatie van ipilimumab (1 mg/kg elke 6 weken) plus nivolumab (3 mg/kg elke 2 weken) ging bij deze patiënten gepaard met een betere algehele overleving dan chemotherapie met cisplatin plus pemetrexed. Bij een mediane follow-up van 43,1 maanden was de overall overleving (OS) 4 maanden langer met ipilimumab plus nivolumab, met een 3-jaars OS van 23% versus 15% voor chemotherapie. Dat klinkt niet erg goed maar longmesothelioma is een agressieve ziekte en de kans dit te overleven is heel klein. 

Figure thumbnail gr1

Figure 1OS in (A) all randomized patients, (B) patients with epithelioid histology, and (C) patients with non-epithelioid histology. CI, confidence interval; HR, hazard ratio; OS, overall survival.

Kernpunten uit deze studie:

  • Met een follow-up van ≥3 jaar in de CheckMate 743 studie, bleef nivolumab + ipilimumab langdurig OS-voordeel opleveren in eerstelijns longmesothelioma.
  • Klinische voordelen bleven consistent in alle subgroepen van patiënten, inclusief epithelioïde versus niet-epithelioïde histologie.
  • Stoppen met nivolumab + ipilimumab vanwege aan de behandeling gerelateerde bijwerkingen had geen negatief effect op het langetermijnvoordeel.
  • Nivolumab + ipilimumab blijft een effectieve eerstelijns behandelingsoptie voor patiënten met inoperabele longmesothelioma.
  • Er zijn drie grotere lopende gerandomiseerde fase III-onderzoeken die chemotherapie en remming van het immuuncheckpoint combineren (NCT03762018, NCT02784171, NCT04334759).

Het studierapport is gratis in te zien. Klik op de titel van het abstract:

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

Open AccessPublished:February 02, 2022DOI:https://doi.org/10.1016/j.annonc.2022.01.074

Highlights

  • With a ≥3-year follow-up in CheckMate 743, nivolumab + ipilimumab continued to provide long-term OS benefit in 1L MPM.
  • Clinical benefits remained consistent across patient subgroups, including epithelioid vs non-epithelioid histology.
  • Discontinuing nivolumab + ipilimumab due to treatment-related adverse events did not negatively impact long-term benefit.
  • Nivolumab + ipilimumab continues to be an efficacious 1L treatment option for patients with unresectable MPM.
  • There are three larger ongoing randomized phase III trials combining chemotherapy and immune checkpoint inhibition (NCT03762018, NCT02784171, NCT04334759).

ABSTRACT

Background

In the phase 3 CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up.

Patients and methods

Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1:1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or 6 cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including 4-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs).

Results

With median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months (HR [95% CI], 0.73 [0.61–0.87]), and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the 4-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for one year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation.

Conclusions

With 3 years’ minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

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