Zie ook literatuurlijst niet-toxische stoffen en weinig belastende behandelingen specifiek bij nierkanker van arts-bioloog drs. Engelbert Valstar.

8 maart 2022: Op ASCO 2022 zijn van onderstaande studie (de Keynote-564 studie) nieuwe gegevens bekend gemaakt die na een follow-up van 30 maanden bevestigen dat pembrolizumab de kans op een recidief voor nierkankerpatiënten met hoog risico op een recidief sterk vermindert. Het vervolgonderzoek werd gepresenteerd op het American Society of Clinical Oncology Genitourinary Cancers Symposium, dat online plaatsvond vanaf februari 17 tot 19 februari 2022. Abstract staat onderaan dit artikel. 

Het geschatte percentage ziektevrije patiënten na 24 maanden was 78,3% met pembrolizumab versus 67,3% met een  placebo. Zie verder het abstract in deze PDF, no. 290.  

23 augustus 2021: N Engl J Med 2021; 385:683-694

Patiënten met nierkanker die een nefrectomie - operatie ondergaan, hebben regulier meestal geen opties voor een aanvullende behandeling om een recidief te voorkomen. Terwijl veel nierkankerpatiënten een groot risico lopen op een recidief.  
Uit een placebo gecontroleerde dubbelblinde garandomiseerde studie blijkt dat preventief immuuntherapie geven om de kansen op een recidief te verminderen met pembrolizumab, een zogeheten anti-PD medicijn, de kans op een recidief vermindert met 9 procent op 2-jaars meting: 77,3 procent versus 68,1 procent. (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval , 0.53 to 0.87; P=0.002 [two-sided]). Dit is statistisch significant aldus de onderzoekers. 

In totaal werden in de studie 496 patiënten willekeurig toegewezen om pembrolizumab te krijgen en 498 patiënten om placebo te krijgen. Patiënten met clearcell nierkanker met een hoog risico op een recidief na een operatie (nefrectomie), met of zonder weghalen van uitzaaiingen, kregen na de operatie ofwel pembrolizumab (in een dosis van 200 mg) ofwel een placebo eenmaal per 3 weken gedurende maximaal 17 cycli ( ongeveer 1 jaar)

Het geschatte percentage patiënten dat na 24 maanden nog in leven was, was 96,6% in de pembrolizumab-groep en 93,5% in de placebogroep. (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96).

Bijwerkingen van graad 3 of hoger, ongeacht de oorzaak, traden op bij 32,4% van de patiënten die pembrolizumab kregen en bij 17,7% van degenen die placebo kregen. Er waren geen sterfgevallen gerelateerd aan de behandeling met pembrolizumab.

Het volledige studierapport is tegen betaling of tegen bepaalde voorwaarden ook gratis in te zien. Klik op de titel van het abstract:

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma

List of authors.
  • Toni K. Choueiri, M.D., 
  • Piotr Tomczak, M.D., Ph.D., 
  • Se Hoon Park, M.D., 
  • Balaji Venugopal, M.D., 
  • Thomas Ferguson, M.D., 
  • Yen-Hwa Chang, M.D., Ph.D., 
  • Jaroslav Hajek, M.U.Dr., 
  • Stefan N. Symeonides, M.D., Ph.D., 
  • Jae Lyun Lee, M.D., Ph.D., 
  • Naveed Sarwar, M.D., Ph.D., 
  • Antoine Thiery-Vuillemin, M.D., Ph.D., 
  • Marine Gross-Goupil, M.D., Ph.D., 
  •  for the KEYNOTE-564 Investigators*

Abstract

BACKGROUND

Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.

METHODS

In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator’s assessment. Overall survival was a key secondary end point. Safety was a secondary end point.

RESULTS

A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval , 0.53 to 0.87; P=0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred.

CONCLUSIONS

Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334. opens in new tab.)

Digital Object ThumbnailQUICK TAKE VIDEO SUMMARYPembrolizumab after Nephrectomy in Renal-Cell Carcinoma 01:47



Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma:

Results from 30-month follow-up of KEYNOTE-564. Toni K. Choueiri, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Tom Ferguson, Stefan N. Symeonides, Jaroslav Hajek, Yen-Hwa Chang, Jae-Lyun Lee, Naveed Sarwar, Antoine ThieryVuillemin, Marine Gross-Goupil, Mauricio Mahave, Naomi B. Haas, Piotr Sawrycki, Lei Xu, Kentaro Imai, Jacqueline Willemann-Rogerio, David I. Quinn, Thomas Powles; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA; Szpital Kliniczny Przemienienia Panskiego UM im. K. Marcinkowskiego, Poznan, Poland; Division of Hematology-Oncology, Samsung Medical Center, Department of Medicine, Seoul, South Korea; University of Glasgow, Glasgow, United Kingdom; Royal Perth Hospital, Perth, Australia; Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom; Fakultni Nemocnice Ostrava, Ostrava, Czech Republic; Taipei Veterans General Hospital, Taipei, Taiwan; Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea; Imperial College Healthcare NHS Trust, London, United Kingdom; University Hospital Jean Minjoz, Besanc¸on, France; Centre Hospitalier Universitaire de Bordeaux-Hopital Saint-Andr ^ e, Bordeaux, France; Lopez Perez Foundation, Santiago, Chile; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu, Warszawa, Poland; Merck & Co., Inc., Upper Gwynedd, PA; Merck & Co., Inc., Kenilworth, NJ; USC Norris Cancer Hospital, Los Angeles, CA; Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, London, United Kingdom

Background: The double-blind, multicenter, randomized KEYNOTE-564 study (NCT03142334) is the first positive phase 3 study of adjuvant immunotherapy for patients (pts) with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions. Adjuvant pembrolizumab resulted in a statistically significant improvement in disease-free survival (DFS) vs placebo with 24 months of follow-up (HR 0.68, 95% CI 0.530.87; P = 0.0010 [one-sided]). We present updated efficacy and safety results from KEYNOTE-564 with 6 months of additional follow-up.

Methods: Pts had histologically confirmed, clear cell RCC (pT2, grade 4 or sarcomatoid, N0 M0; pT3 or pT4, any grade, N0 M0; any pT, any grade, N+ M0; or M1 NED [no evidence of disease after primary tumor and soft tissue metastases completely resected ≤1 year from nephrectomy]) and had undergone surgery ≤12 weeks prior to randomization. The primary endpoint was DFS by investigator assessment in all randomized pts (ITT population). Overall survival (OS) was a key secondary endpoint. Safety/tolerability in all treated pts was a secondary endpoint.

Results: 994 pts were randomized 1:1 to pembrolizumab (N = 496) or placebo (N = 498). As of data cutoff date of June 14, 2021, median (range) follow-up, defined as time from randomization to data cutoff, was 30.1 (20.847.5) months. In this updated analysis, DFS benefit with pembrolizumab was maintained (HR 0.63, 95% CI 0.500.80; nominal P < 0.0001) and was consistent across subgroups, including pts with M0 disease with intermediate-high risk of recurrence (HR 0.68, 95% CI 0.520.89), M0 high risk of recurrence (HR 0.60, 95% CI 0.331.10), or M1 NED (HR 0.28, 95% CI 0.120.66). The estimated DFS rate at 24 months was 78.3% with pembrolizumab vs 67.3% with placebo. A total of 66 OS events were observed, 23 in the pembrolizumab arm and 43 in the placebo arm (HR 0.52, 95% CI 0.310.86; P = 0.0048); the p-value did not cross the statistical hypothesis testing boundary and additional follow-up is planned for this key secondary endpoint. The estimated OS rate at 24 months was 96.2% with pembrolizumab vs 93.8% with placebo. With additional follow-up, no increase in any-grade or grade 3-4 adverse events, or steroid use for immune-mediated adverse events was observed. No deaths related to pembrolizumab occurred.

Conclusions: At 30 months of follow-up, adjuvant pembrolizumab continued to demonstrate a consistent and clinically meaningful improvement in DFS vs placebo in pts with RCC at high risk of recurrence. No new safety signals were observed with pembrolizumab in the adjuvant setting. Clinical trial information: NCT03142334. Research Sponsor: Merck & Co, Inc.

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