14 september 2017:

op ESMO 2017 is onderstaande studie gepresenteerd met deze resultaten. klik op de volgende link voor volledige tekst: CheckMate-214, combined nivolumab and ipilimumab shows considerable benefit in intermediate- and poor-risk patients with advanced or metastatic renal cell carcinoma

...............

The benefit from the immunotherapy combination in intermediate/high risk patients

After approximately 17.5 months of follow-up, CheckMate-214 met the co-primary endpoint of ORR in intermediate/poor risk patients, which was 41.6% for the nivolumab/ipilimumab combination compared to 26.5% for sunitinib (p < 0.0001) with 9.4% of patients receiving combination therapy achieving complete response (CR) compared to1.2% of patients on sunitinib.

The median duration of response (DoR) was not reached (95% confidence interval 21.82, NR) versus 18.2 months with sunitinib (95% CI 14.82, NR).

There was an improvement in median PFS with the combination in this cohort;median PFS was 11.6 months for the nivolumab and ipilimumab combination versus 8.4 months with sunitinib, hazard ratio 0.82 (p = 0.03).

The efficacy outcomes differed according to the levels of PD-L1 expression and IMDC risk group

Both the ORR per indipendent committee and PFS significantly favoured nivolumab plus ipilimumab over sunitinib in intermediate/poor risk patients having baseline PD-L1 expression ≥1% where the ORR was 58% versus 25%, and median PFS was 22.8 (95% CI 9.4, NR) months versus 5.9 (95% CI 4.4, 7,1) months, respectively, HR 0.48 (95% CI 0.28, 0.82; p = 0.0003).

The investigators found that baseline tumour PD-L1 expression was lower in the cohort of patients at favourable risk where 11% of patients on combination had PD-L1 levels ≥1% versus12% of patients on sunitinib compared to 26% versus 29% of patients at intermediate or poor risk in the respective treatment arms. Lees volledige artikel verder>>>>>>

24 augustus 2017: Lees ook dit artikel: 

https://kanker-actueel.nl/NL/nivolumab-een-immuuntherapeutisch-anti-pd-medicijn-geeft-uitstekende-resultaten-bij-vergevorderde-nierkanker-versus-everolimus-en-krijgt-van-fda-goedkeuring-voor-gebruik-als-medicijn.html

24 augustus 2017: Bron: Bristol-Myers Squibb persbericht en Journal of Clinical Oncology 33,

Ook bij gevorderde uitgezaaide nierkanker blijkt immuuntherapie met zowel alleen nivolumab (Opvio) als nivolumab in combinatie met ipilimumab (Yervoy) hoopgevende en uitstekende resultaten te geven op progressievrije ziekte en overall overleving.

Afgelopen maand gaf Bristol-Myers Squibb een persbericht uit waarin zij schrijven dat de tussenresultaten uit de Chckmate-214 fase III studie waarin patiënten opgenomen in alle stadia, sommige waren al voorbehandeld, anderen nog helemaal niet, uitstekende resultaten geven. Doel van deze studie is te kijken of deze combinatietherapie straks gegeven kan worden als eerstelijns behandeling.

Ter vergelijking hier een grafiek van overall overleving en progressievrije ziekte met verschillende behandelingen bij niercelkanker uit deze studie: Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy waaruit zou blijken dat targeted therapie betere resultaten geeft dan immuuntherapie. Maar studies met zwaarvoorbehandelde vergevorderde kanker geven andere resultaten dan na een eerste diagnose en met weinig of geen tumorload.

(tekst loopt verder onder grafiek):

niercelkanker overall vergelijkling van behandelingen

In het persbericht schrijven de mensen van BMS:

Bristol-Myers Squibb Company (NYSE: BMY) kondigt vandaag de topline resultaten aan van de CheckMate -214 trial Opdivo (nivolumab) in combinatie met Yervoy (ipilimumab) versus sunitinib bij intermediaire en laag risico patiënten met eerder onbehandelde of gevorderde of uitgezaaide niercelcarcinoom. 

De combinatie voldoet aan het co-primaire einddoel van de objectieve respons (ORR) en bereikte een 41,6% ORR versus 26,5% voor sunitinib. De mediane duur van de respons is nog niet bereikt voor de combinatie van Opdivo en Yervoy en was 18,17 maanden voor sunitinib. Terwijl er een verbetering was in de voortgangsvrije overleving (PFS) (HR = 0,82, [99,1% CI 0,64-1,05], gestratificeerd 2-zijdig p = 0,03), was deze nog niet statistisch significant. De mediane PFS was 11,56 maanden (95% CI 8,71 - 15,51) voor de Opdivo en Yervoy combinatie versus 8.38 maanden (95% CI 7.03-10.81) voor sunitinib. De studie zal zoals gepland doorlopen, om het derde co-primaire einddoel van OS - overall overleving te meten. Het bijwerkrngenprofiel in de CheckMate-214 studie was consistent met dat waargenomen in eerder gemelde studies met dit doseringsschema.

Volgens het persbericht voldoet deze studie aan de verwachtingen dat nivolumab plus ipilumumab over enkele jaren eerste lijns kan wroden waar nu nivolumab al is geodgekeurd als tweedelijns voor niercelkanker.

Want in deze studie: Updated survival results from a randomized, dose-ranging phase II study of nivolumab (NIVO) in metastatic renal cell carcinoma (mRCC). blijkt nivolumab ook bij voorbehandelde gevorderde uitgezaaide nierkanker uitstekende resultaten te geven.

NIVO, Q3W
0.3 mg/kg
n = 59
2 mg/kg
n = 54
10 mg/kg
n = 54
Median OS, mo
(80% CI)
18.5 (16.7–NA) 25.5 (19.8–31.2) 24.8 (15.3–26.0)
OS rate, %
12 mo 63 72 70
24 mo 42 53 52
36 mo 33 40 32

Inmiddels is een fase III studie opgestart: Clinical trial information: NCT01354431.

Het originele persbericht kunt u lezen als u op de volgende link klikt: Bristol-Myers Squibb Announces Topline Results from CheckMate -214, a Phase 3 Study of Opdivo in Combination with Yervoy in Intermediate and Poor-Risk Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

Het abstract van deze studie, waarvan het volledige studierapprot gratis is in te zien: Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy  staat hieronder met ook een referentielijst:

In patients with mRCC - metastatic renal cell carcinoma targeted therapy provided a better PFS and OS compared with immunotherapy

Cancer Res Treat. 2016 Jul; 48(3): 1092–1101.
Published online 2016 Jan 28. doi:  10.4143/crt.2015.316
PMCID: PMC4946361

Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy

Sung Han Kim, MD, PhD,1 Weon Seo Park, MD, PhD,1,2 Sun Ho Kim, MD, PhD,3 Jae Young Joung, MD, PhD,1 Ho Kyung Seo, MD, PhD,1 Kang Hyun Lee, MD, PhD,1 and Jinsoo Chung, MD, PhD1

Abstract

Purpose

The purpose of this study is to compare the outcomes of first-line systemic targeted therapy (TT) and immunotherapy (IT) in patients with metastatic renal cell carcinoma (mRCC).

Materials and Methods

This study was a retrospective review of the data of 262 patients treated with systemic IT or TT with tyrosine kinase inhibitors between 2003 and 2013. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using Response Evaluation Criteria in Solid Tumor ver. 1.0 criteria and the Kaplan-Meier method with log-rank test.

Results

During the median 4.3-month treatment and the 24-month follow-up period, the ORR/PFS/OS of the overall first-line and second-line therapy were 41.9%/8.1 months/16.8 months and 27.5%/6.5 months/15.3 months, respectively. The first-line TT/IT/sequential IT had a PFS of 9.3/6.4/5.7 months and an OS of 15.8/16.5/40.6 months (all p < 0.05). The second-line of TT/IT had a PFS of 7.1/2.1 months (both p < 0.05) and an OS of 16.6/8.6 months (p=0.636), respectively. Pazopanib provided the best median PFS of 11.0 months (p < 0.001) and a quadruple IT regimen had a superior PFS (p=0.522). For OS, sequential treatment with IT and TT was superior compared to treatment with either IT or TT alone (40.6/16.5/15.8 months, p=0.014). The prognosis according to the Memorial Sloan Kettering Cancer Center model showed that favorable/intermediate/poor risk groups had a PFS of 8.5/10.4/2.3 months, and an OS of 43.1/20.4/5.6 months, respectively. The prognosis calculated using the Heng model showed that the favorable/intermediate/poor risk groups had a PFS of 9.2/3.9/2.7 months, and an OS of 32.4/16.5/6.1months, respectively (all p < 0.001).

Conclusion

In patients with mRCC, TT provided a better PFS and OS compared with IT.

References

1. Motzer RJ, Agarwal N, Beard C, Bolger GB, Boston B, Carducci MA, et al. NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Canc Netw. 2009;7:618–30. [PubMed]
2. Oudard S, George D, Medioni J, Motzer R. Treatment options in renal cell carcinoma: past, present and future. Ann Oncol. 2007;18 Suppl 10:x25–31. [PubMed]
3. Fossa SD, Raabe N, Moe B. Recombinant interferon-alpha with or without vinblastine in metastatic renal carcinoma: results of a randomised phase II study. Br J Urol. 1989;64:468–71. [PubMed]
4. Pyrhonen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T, et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999;17:2859–67. [PubMed]
5. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6 Suppl 1:S55–7. [PubMed]
6. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13:688–96. [PubMed]
7. Cho IC, Chung J. Current status of targeted therapy for advanced renal cell carcinoma. Korean J Urol. 2012;53:217–28. [PMC free article] [PubMed]
8. Lee JH, Chang SG, Jeon SH, Min GE, Yoo KH. Comparative analysis between immunochemotherapy and target therapy for metastatic renal cell carcinoma: overview of treatment-related adverse events and the dropout rate in Korea. Korean J Urol. 2010;51:379–85. [PMC free article] [PubMed]
9. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, 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;27:5794–9. [PubMed]
10. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–96. [PubMed]
11. Motzer RJ, Russo P. Systemic therapy for renal cell carcinoma. J Urol. 2000;163:408–17. [PubMed]
12. McDermott DF. Update on the application of interleukin-2 in the treatment of renal cell carcinoma. Clin Cancer Res. 2007;13(2 Pt 2):716s–20s. [PubMed]
13. Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1280–9. [PubMed]
14. Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28:475–80. [PubMed]
15. Desai AA, Stadler WM. Novel kinase inhibitors in renal cell carcinoma: progressive development of static agents. Curr Urol Rep. 2006;7:16–22. [PubMed]
16. Akaza H, Naito S, Ueno N, Aoki K, Houzawa H, Pitman Lowenthal S, et al. Real-world use of sunitinib in Japanese patients with advanced renal cell carcinoma: efficacy, safety and biomarker analyses in 1689 consecutive patients. Jpn J Clin Oncol. 2015;45:576–83. [PMC free article] [PubMed]
17. Akaza H, Oya M, Iijima M, Hyodo I, Gemma A, Itoh H, et al. A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance. Jpn J Clin Oncol. 2015;45:953–62. [PMC free article] [PubMed]
18. Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma. Br J Cancer. 2015;113:12–9. [PMC free article] [PubMed]
19. Albiges L, Oudard S, Negrier S, Caty A, Gravis G, Joly F, et al. Complete remission with tyrosine kinase inhibitors in renal cell carcinoma. J Clin Oncol. 2012;30:482–7. [PubMed]
20. Johannsen M, Staehler M, Ohlmann CH, Florcken A, Schmittel A, Otto T, et al. Outcome of treatment discontinuation in patients with metastatic renal cell carcinoma and no evidence of disease following targeted therapy with or without metastasectomy. Ann Oncol. 2011;22:657–63. [PubMed]
21. Matrana MR, Bathala T, Campbell MT, Duran C, Shetty A, Teegavarapu P, et al. Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with front-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) or mammalian target of rapamycin inhibitors (mTORi): a single institution experience. BJU Int. 2015 Nov 17; . http://dx.doi.org/10.1111/bju.13374. [PMC free article] [PubMed]
22. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34. [PubMed]
23. Ward E, Jemal A, Cokkinides V, Singh GK, Cardinez C, Ghafoor A, et al. Cancer disparities by race/ethnicity and socioeconomic status. CA Cancer J Clin. 2004;54:78–93. [PubMed]
24. Sadeghi S, Albiges L, Wood LS, Black SL, Gilligan TD, Dreicer R, et al. Cessation of vascular endothelial growth factor-targeted therapy in patients with metastatic renal cell carcinoma: feasibility and clinical outcome. Cancer. 2012;118:3277–82. [PubMed]

Articles from Cancer Research and Treatment : Official Journal of Korean Cancer Association are provided here courtesy of Korean Cancer Association

References belonging to nivolumab studies

Een referentielijst van eerdere studies staat hier:

Literatur

  1. 1.
    Schmiedinger M, Bellmunt J (2010) Plethora of agents, plethora of targets, plethora of side effects in metastatic renal cell carcinoma. Cancer Treat Rev 36:416–424CrossRefGoogle Scholar
  2. 2.
    Motzer RJ, Hutson TE, McCann L et al (2014) Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med 370:1769–1780CrossRefPubMedGoogle Scholar
  3. 3.
    Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731CrossRefPubMedGoogle Scholar
  4. 4.
    Motzer RJ, Escudier B, Oudard S et al (2014) Phase II randomized trial comparing sequential first-line everolimus and second-line Sunitinib versus first-line Sunitinib and second-line Everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 32:2765–2772CrossRefPubMedGoogle Scholar
  5. 5.
    Postow MA, Callahan MK, Wolchok JD (2014) Immune checkpoint blockade in cancer therapy. J Clin Oncol 32: 1020–1030. doi:10.1200/JCO.2014.59.4358CrossRefGoogle Scholar
  6. 6.
    Michel MS, Vervenne W, de Santis M et al (2014) SWITCH study of efficacy and safety of Sorafenib/Sunitinib vs. Sunitinib/Sorafenib in the treatment of mRCC. J Clin Oncol 32(Suppl 4):393Google Scholar
  7. 7.
    Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med 363:711–723PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Plimack ER, Hammers HJ, Rini BI et al (2015) Updated survival results from a randomized, dose-ranging phase II study of nivolumab (NIVO) in metastatic renal cell carcinoma (mRCC). Clin J Oncol 33(Suppl):4553Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Plaats een reactie ...

Reageer op "Nivolumab (Obvio) alleen en samen met ipilimumab (Yervoy) geeft uitstekende resultaten bij gevorderde niercelkanker ook in vergelijking met sunitinib"


Gerelateerde artikelen