Immuuncheckpointremmers nivolumab + ipilimumab of pembrolizumab + axitinib geeft toch ziektecontrole en remissies in de klinische praktijk bij patiënten met gevorderde uitgezaaide nierkanker met een slechte prestatiestatus volgens ECOG PS ≥2

18 januari 2023: Bron: European Journal of Cancer Published 1 februari 2023

Omdat bij grotere fase II en fase III studies nierkankerpatiënten met een slechte prestatiescore meestal niet in aanmerking voor deelname zijn er ook weinig gegevens of bv immuuntherapie wel zinvol zou zijn. Een retrospectief onderzoek in meerdere ziekenhuizen uitgevoerd op data van nierkankerpatiënten met uitgezaaide gevorderde clearcel nierkanker met een slechte ECOG-prestatie status te weten PS ≥2, die een eerstelijns behandeling hadden gehad in de klinische praktijk op basis van immuuncheckpointremmers nivolumab + ipilimumab (PI) of pembrolizumab + axitinib (AP) liet zien dat hoewel zij minder scoorden dan patiënten uit studies met een betere prestatiescore zij toch redelijk goed reageerden.

De mediane progressievrije overleving (PFS) was 5,4 maanden en de mediane totale overleving (OS) was 16,0 maanden en het objectieve responspercentage (ORR) was 31%.

Alle resultaten uit het abstract vertaald:

We identificeerden 70 mRCC-patiënten met PS ≥2 die werden behandeld met een op immuuntherapie met checkpointremmers (ICI) gebaseerde combinatiebehandeling in 14 instellingen tussen oktober 2017 en december 2021, waaronder 45 en 25 patiënten die werden behandeld met respectievelijk nivolumab + ipilimumab (PI) en pembrolizumab + axitinib (AP).
De mediane leeftijd bij diagnose was 63 jaar, 51 (73%) waren man, slechts 17 (24%) hadden eerdere nefrectomie (operatie) ondergaan, 50 (71%) hadden synchrone uitgezaaide ziekte bij 1e diagnose en 16 (23%) hadden hersenmetastasen.
Eenenzestig (87%) en 9 (13%) patiënten hadden respectievelijk ECOG (Eastern Cooperative Oncology Group) PS 2 en 3, en 25 (36%) en 45 (64%) patiënten waren intermediair en slechte prognose volgens de International Metastatic RCC Database Consortium (IMDC).
Van alle patiënten was 91% clear cell RCC, 7 patiënten hadden sarcomatoïde kenmerken.
Op het moment van de analyse (mediane follow-up 11,1 maanden) was 41% van de patiënten overleden.
De mediane PFS en mOS in het gehele cohort waren respectievelijk 5,4 maanden en 16,0 maanden; ORR was 31%.
Er werden geen significante verschillen in ORR, PFS, OS of G ≥3AE's gezien tussen NI en AP.
De intermediaire en slechte IPI-groepen waren significant geassocieerd met verminderde ORR en kortere PFS.

Voor een volledig studierapport moet worden betaald. Maar hier het originele abstract plus referentielijst:

ORIGINAL RESEARCH| VOLUME 180, P21-29, FEBRUARY 01, 2023

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

Published:December 16, 2022DOI:https://doi.org/10.1016/j.ejca.2022.11.013

Highlights

•
First cohort of poor PS mRCC treated with front line ICI-based combination therapy.
•
The survival outcomes were inferior to that reported in pivotal trials.
•
No significant differences in ORR, PFS or OS were seen between NI and AP.
•
Both NI and AP were well tolerated without significant differences between them.

Abstract

Background

Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown.

Methods

We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated.

Results

We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS.

Conclusion

We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results.

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