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

Update artikel: 10 februari 2024:

Uit nieuwe studiegegevens van de Keynote-564 studie (een placebo gecontroleerde fase III studie bij patiënten met operabele nierkanker maar wel met groot risico op een recidief), blijkt dat na een follow-up van mediaan 57,2 maanden een significante verbetering in de algehele overleving met pembrolizumab werd bereikt.

Pembrolizumab is een vorm van immuuntherapie met een anti-PD medicijn ook wel checkpointremmer genoemd.
Na 48 maanden was het geschatte totale overlevingspercentage 91,2 procent in de pembrolizumab-groep versus 86,0 procent in de placebo-groep.
De onderzoekers zagen het overlevingsvoordeel in verschillende subgroepen, ongeacht het stadium van de ziekte, de risicostratificatie, immunologische biomarkers of andere kenmerken.

Ongeveer 18 procent van de patiënten stopte met de behandeling vanwege bijwerkingen gerelateerd aan pembrolizumab.

“We kunnen onze patiënten nu vertellen dat pembrolizumab na een operatie niet alleen recidieven vertraagt, maar hen ook helpt langer te leven”, zei onderzoeksleider Toni Choueiri MD. in een persbericht.

Klik hier voor het abstract zoals gepresenteerd op ASCO 2024. Abstract staat ook onderaan artikel.

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

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.)

QUICK 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.

Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC).

Authors

Toni K. Choueiri, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Thomas Ferguson, Stefan N. Symeonides, Jaroslav Hajek, Yen-Hwa Chang, Jae-Lyun Lee, Naveed Sarwar, Howard Gurney, Marine Gross-Goupil, Mauricio Mahave, Naomi B. Haas, Piotr Sawrycki, Tian Zhang, Jerry Cornell, Aymen Elfiky, Joseph E. Burgents, Thomas Powles

Organizations

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Poznan University of Medical Sciences, Poznan, Poland, Sungkyunkwan University, Samsung Medical Center, Seoul, Korea, Republic of (South), Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United Kingdom, Fiona Stanley Hospital, Perth, Western Australia, Australia, Edinburgh Cancer Centre and University of Edinburgh, Edinburgh, United Kingdom, Fakultni Nemocnice Ostrava, Ostrava, Czech Republic, Taipei Veterans General Hospital, Taipei, Taiwan, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Imperial College Healthcare NHS Trust, London, United Kingdom, Macquarie University Hospital, Sydney, NSW, Australia, Centre Hospitalier Universitaire de Bordeaux - Hôpital Saint-André, Bordeaux, France, Fundacion Arturo Lopez Perez FALP, Santiago, Chile, Abramson Cancer Center, Penn Medicine, Philadelphia, PA, Provincial Hospital in Torun, Torun, Poland, University of Texas Southwestern Medical Center, Dallas, TX, Merck & Co., Inc., Rahway, NJ, Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, and Queen Mary University of London, London, United Kingdom

Abstract Disclosures

Research Funding

Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

Background:

The randomized, multicenter, double-blind, phase 3 KEYNOTE-564 study (NCT03142334) showed that adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo following nephrectomy in participants (pts) with ccRCC at an increased risk of recurrence. We report results from the third prespecified interim analysis with a median follow-up of ~57 months.

Methods:

Pts were aged ≥18 years and had histologically confirmed ccRCC with or without sarcomatoid features, increased risk of recurrence, ECOG PS of 0 or 1, nephrectomy and/or metastasectomy ≤12 weeks before randomization, and no prior systemic therapy for RCC. Pts were randomly allocated 1:1 to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≥17 cycles (~1 year) or until disease recurrence, intolerable toxicity, or withdrawal of consent. DFS by investigator assessment was the primary end point. Overall survival (OS) was a key secondary end point. Safety was a secondary end point.

Results:

994 pts were randomized 1:1 to pembrolizumab (n=496) or placebo (n=498). The median time from randomization to data cut-off date of September 15, 2023, was 57.2 months (range, 47.9−74.5). Statistically significant improvement in OS was observed with pembrolizumab vs placebo (medians not reached, HR 0.62, 95% CI 0.44−0.87; P=.0024). A total of 55 OS events were observed in the pembrolizumab arm and 86 in the placebo arm. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86.0% with placebo. OS benefit was observed across key subgroups, including in pts with M0 disease (HR 0.63, 95% CI 0.44−0.90) or M1 NED (HR 0.51, 95% CI 0.15−1.75), with PD-L1 CPS <1 (HR 0.65, 95% CI 0.31−1.38) or CPS ≥1 (HR 0.62, 95% CI 0.42−0.91), and with presence (HR 0.69, 95% CI 0.28−1.70) or absence (HR 0.57, 95% CI 0.39−0.84) of sarcomatoid features. The observed DFS benefit with pembrolizumab vs placebo was consistent with prior interim analyses (HR 0.72; 95% CI 0.59−0.87). No new safety signals were observed.

Conclusions:

After a median of ~57 months of follow-up, adjuvant pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in overall survival versus placebo in participants with RCC at increased risk of recurrence post surgery. KEYNOTE-564 is the first phase 3 study to show improved survival with any adjuvant therapy in RCC. These results continue to support adjuvant pembrolizumab as a standard of care. Clinical trial information: NCT03142334.