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 180P21-29, FEBRUARY 01, 2023
Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

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.

References

    • Escudier B.
    • Porta C.
    • Schmidinger M.
    • Rioux-Leclercq N.
    • Bex A.
    • Khoo V.
    • et al.
    Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
    Ann Oncol. 2019 May; 30706-720
    • Choueiri T.K.
    • Powles T.
    • Burotto M.
    • Escudier B.
    • Bourlon M.T.
    • Zurawski B.
    • et al.
    Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma.
    N Engl J Med. 2021 Mar 4; 384829-841
    • Motzer R.
    • Alekseev B.
    • Rha S.Y.
    • Porta C.
    • Eto M.
    • Powles T.
    • et al.
    Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma.
    N Engl J Med. 2021 Apr 8; 3841289-1300
    • Motzer R.J.
    • Tannir N.M.
    • McDermott D.F.
    • Arén Frontera O.
    • Melichar B.
    • Choueiri T.K.
    • et al.
    Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.
    N Engl J Med. 2018 Apr 5; 3781277-1290
    • Rini B.I.
    • Plimack E.R.
    • Stus V.
    • Gafanov R.
    • Hawkins R.
    • Nosov D.
    • et al.
    Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
    N Engl J Med. 2019 Mar 21; 3801116-1127
    • Sok M.
    • Zavrl M.
    • Greif B.
    • Srpčič M.
    Objective assessment of WHO/ECOG performance status.
    Support Care Cancer. 2019 Oct; 273793-3798
    • Scott J.M.
    • Stene G.
    • Edvardsen E.
    • Jones L.W.
    Performance status in cancer: not broken, but time for an upgrade?.
    J Clin Orthod. 2020 Sep 1; 382824-2829
    • Bellmunt J.
    • Choueiri T.K.
    • Fougeray R.
    • Schutz F.A.B.
    • Salhi Y.
    • Winquist E.
    • et al.
    Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens.
    J Clin Oncol. 2010 Apr 10; 281850-1855
    • Xu Y.
    • Zhang Y.
    • Wang X.
    • Kang J.
    • Liu X.
    Prognostic value of performance status in metastatic renal cell carcinoma patients receiving tyrosine kinase inhibitors: a systematic review and meta-analysis.
    BMC Cancer. 2019 Dec; 19168
    • Jang R.W.
    • Caraiscos V.B.
    • Swami N.
    • Banerjee S.
    • Mak E.
    • Kaya E.
    • et al.
    Simple prognostic model for patients with advanced cancer based on performance status.
    JOP. 2014 Sep; 10e335-e341
    • Motzer R.J.
    • Bacik J.
    • Murphy B.A.
    • Russo P.
    • Mazumdar M.
    Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.
    J Clin Orthod. 2002 Jan 1; 20289-296
    • Heng D.Y.
    • Xie W.
    • Regan M.M.
    • Harshman L.C.
    • Bjarnason G.A.
    • Vaishampayan U.N.
    • et al.
    External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study.
    Lancet Oncol. 2013 Feb; 14141-148
    • Heng D.Y.C.
    • Xie W.
    • Regan M.M.
    • Warren M.A.
    • Golshayan A.R.
    • Sahi C.
    • et al.
    Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.
    J Clin Oncol. 2009 Dec 1; 275794-5799
    • Ahmed T.
    • Lycan T.
    • Dothard A.
    • Ehrlichman P.
    • Ruiz J.
    • Farris M.
    • et al.
    Performance status and age as predictors of immunotherapy outcomes in advanced non-small-cell lung cancer.
    Clin Lung Cancer. 2020 Jul; 21e286-e293
    • Facchinetti F.
    • Mazzaschi G.
    • Barbieri F.
    • Passiglia F.
    • Mazzoni F.
    • Berardi R.
    • et al.
    First-line pembrolizumab in advanced non–small cell lung cancer patients with poor performance status.
    Eur J Cancer. 2020 May 1; 130155-167
    • Khaki A.R.
    • Li A.
    • Diamantopoulos L.N.
    • Bilen M.A.
    • Santos V.
    • Esther J.
    • et al.
    Impact of performance status on treatment outcomes: a real-world study of advanced urothelial cancer treated with immune checkpoint inhibitors.
    Cancer. 2020 Mar 15; 1261208-1216
    • Yang F.
    • Markovic S.N.
    • Molina J.R.
    • Halfdanarson T.R.
    • Pagliaro L.C.
    • Chintakuntlawar A.V.
    • et al.
    Association of sex, age, and Eastern Cooperative Oncology Group performance status with survival benefit of cancer immunotherapy in randomized clinical trials: a systematic review and meta-analysis.
    JAMA Netw Open. 2020 Aug 3; 3e2012534
    • Bersanelli M.
    • Brighenti M.
    • Buti S.
    • Barni S.
    • Petrelli F.
    Patient performance status and cancer immunotherapy efficacy: a meta-analysis.
    Med Oncol. 2018 Aug 20; 35132
    • Alessi J.V.
    • Ricciuti B.
    • Jiménez-Aguilar E.
    • Hong F.
    • Wei Z.
    • Nishino M.
    • et al.
    Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status.
    J Immunother Cancer. 2020 Aug 4; 8 () ([cited 2021 Jan 24]. Available from:)
    • Butaney M.
    • Satkunasivam R.
    • Goldberg H.
    • Freedland S.J.
    • Patel S.P.
    • Hamid O.
    • et al.
    Analysis of heterogeneity in survival benefit of immunotherapy in oncology according to patient demographics and performance status: a systematic review and meta-analysis of overall survival data.
    Am J Clin Oncol. 2020 Mar; 43193-202
    • Friedlaender A.
    • Banna G.L.
    • Buffoni L.
    • Addeo A.
    Poor-performance status assessment of patients with non-small cell lung cancer remains vague and blurred in the immunotherapy era.
    Curr Oncol Rep. 2019 Nov 25; 21107
    • Kaira K.
    • Imai H.
    • Mouri A.
    • Yamaguchi O.
    • Kagamu H.
    Clinical effectiveness of immune checkpoint inhibitors in non-small-cell lung cancer with a poor performance status.
    Medicina. 2021 Nov 19; 571273
    • Spigel D.R.
    • McCleod M.
    • Jotte R.M.
    • Einhorn L.
    • Horn L.
    • Waterhouse D.M.
    • et al.
    Safety, efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non–small cell lung cancer, including patients aged 70 years or older or with poor performance status (CheckMate 153).
    J Thorac Oncol. 2019 Sep; 141628-1639
    • Kano H.
    • Ichihara E.
    • Harada D.
    • Inoue K.
    • Kayatani H.
    • Hosokawa S.
    • et al.
    Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status.
    Cancer Sci. 2020 Oct; 1113739-3746
    • Friedlaender A.
    • Metro G.
    • Signorelli D.
    • Gili A.
    • Economopoulou P.
    • Roila F.
    • et al.
    Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab.
    Acta Oncol. 2020 Sep 1; 591058-1063
    • Wong A.
    • Williams M.
    • Milne D.
    • Morris K.
    • Lau P.
    • Spruyt O.
    • et al.
    Clinical and palliative care outcomes for patients of poor performance status treated with antiprogrammed death-1 monoclonal antibodies for advanced melanoma.
    Asia Pac J Clin Oncol. 2017 Dec; 13385-390
    • Asher N.
    • Ben-Betzalel G.
    • Lev-Ari S.
    • Shapira-Frommer R.
    • Steinberg-Silman Y.
    • Gochman N.
    • et al.
    Real world outcomes of ipilimumab and nivolumab in patients with metastatic melanoma.
    Cancers. 2020 Aug 18; 12 () ([cited 2021 Jan 24]. Available from:)
    • Wang L.
    • Shen Y.
    Imbalance of circulating T-lymphocyte subpopulation in gastric cancer patients correlated with performance status.
    Clin Lab. 2013; 59429-433
    • Petrillo L.A.
    • El-Jawahri A.
    • Nipp R.D.
    • Lichtenstein M.R.L.
    • Durbin S.M.
    • Reynolds K.L.
    • et al.
    Performance status and end-of-life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors.
    Cancer. 2020 May 15; 1262288-2295
    • Sehgal K.
    • Gill R.R.
    • Widick P.
    • Bindal P.
    • McDonald D.C.
    • Shea M.
    • et al.
    Association of performance status with survival in patients with advanced non–small cell lung cancer treated with pembrolizumab monotherapy.
    JAMA Netw Open. 2021 Feb 11; 4e2037120
    • Sternberg C.N.
    • Loriot Y.
    • James N.
    • Choy E.
    • Castellano D.
    • Lopez-Rios F.
    • et al.
    Primary results from SAUL, a multinational single-arm safety study of atezolizumab therapy for locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract.
    Eur Urol. 2019 Jul; 7673-81
    • Middleton G.
    • Brock K.
    • Savage J.
    • Mant R.
    • Summers Y.
    • Connibear J.
    • et al.
    Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial.
    Lancet Respir Med. 2020 Sep; 8895-904
    • Felip E.
    • Ardizzoni A.
    • Ciuleanu T.
    • Cobo M.
    • Laktionov K.
    • Szilasi M.
    • et al.
    CheckMate 171: a phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations.
    Eur J Cancer. 2020 Mar; 127160-172
    • Mezquita L.
    • Auclin E.
    • Ferrara R.
    • Charrier M.
    • Remon J.
    • Planchard D.
    • et al.
    Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non–small cell lung cancer.
    JAMA Oncol. 2018 Mar 1; 4351
    • Meyers Stukalin
    • Vallerand Lewinson
    • Suo Dean
    • et al.
    The lung immune prognostic index discriminates survival outcomes in patients with solid tumors treated with immune checkpoint inhibitors.
    Cancers. 2019 Nov 2; 111713
    • Lavaud P.
    • Dalban C.
    • Negrier S.
    • Chevreau C.
    • Gravis G.
    • Oudard S.
    • et al.
    Validation of the lung immune prognostic index (LIPI) in patients with metastatic renal cell carcinoma treated with nivolumab in the GETUG-AFU 26 NIVOREN trial.
    J Clin Orthod. 2020 Feb 20; 38735








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