1L for adjuvant RCC
KEYNOTE-564: A LANDMARK, MULTICENTER,
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL1
KEYTRUDA® as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Watch this short video in which Dr. Seront explains the KEYNOTE-564 study and discusses the most recent clinical data presented at ASCO GU 2022.
STUDY DESIGN: A LANDMARK, MULTICENTER, RANDOMIZED,
DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL1
Primary efficacy outcome measures:
Investigator-assessed disease-free survival (DFS). Median follow-up time: 30.1 months (range: 20.8-47.5 months)
Key secondary outcome measure:
Overall survival (OS)
ECOG PS = Eastern Cooperative Oncology Group performance status; M1 = with distant metastases; Q3W =every 3 weeks; RCC = renal cell carcinoma; pT = primary tumor; M0 = no metastasis; N0 = no regional lymph node metastasis; N1 = involvement of regional lymph nodes; NED = no evidence of disease
Patient characteristics at inclusion in the KN-564 study1
| Characteristic | Pembrolizumab (N=496) | Placebo (N = 498) |
|---|---|---|
| Age | ||
| Median (range) – yr | 60.0 (27−81) | 60.0 (25−84) |
| ≥65 yr – no. (%) | 158 (31.9) | 172 (34.5) |
| Male sex – no. (%) | 347 (70.0) | 359 (72.1) |
| ECOG performance-status score of 1 – no. (%)† | 75 (15.1) | 72 (14.5) |
| Geographic location | ||
| North America | 133 (26.8) | 125 (25.1) |
| European Union‡ | 188 (37.9) | 187 (37.6) |
| Rest of the world | 175 (35.3) | 186 (37.3) |
| Radical nephrectomy – no. (%) | 459 (92.5) | 460 (92.4) |
| Sarcomatoid features – no. (%) | ||
| Present | 52 (10.5) | 59 (11.8) |
| Absent | 417 (84.1) | 415 (83.3) |
| Unknown | 27 (5.4) | 24 (4.8) |
| Disease risk category no. (%)§ | ||
| M0, intermediate-to-high risk | 427 (86.1) | 433 (86.9) |
| M0, high risk | 40 (8.1) | 36 (7.2) |
| M1 NED⁋ | 29 (5.8) | 29 (5.8) |
| PD-L1 combined positive score – no. (%)Ⅱ | ||
| <1 | 124 (25.0) | 113 (22.7) |
| ≥1 | 365 (73.6) | 383 (76.9) |
| Missing data | 7 (1.4) | 2 (0.4) |
ECOG = Eastern Cooperative Oncology Group; M0 = no metastasis; M1 = distant metastasis; PD-L1 = programmed death ligand 1;
N0 = no regional lymph node metastasis; NED = no evidence of disease; † Eastern Cooperative Oncology Group (ECOG) performance-status scores are on a scale from 0 to 5, with higher scores indicating greater disability. A score of 1 indicates that strenuous physical activity is restricted but that the patient is fully ambulatory and able to carry out light work. ‡ The European Union included the United Kingdom at the time of the trial. § Patients with M0 (no metastases) disease and an intermediate-to-high risk of recurrence had disease staged as pT2 (grade 4 tumor or sarcomatoid), N0 (no nodal involvement), M0 or as pT3 (any grade), N0, M0. Patients with M0 disease and a high risk of recurrence had disease staged as pT4 (any grade of tumor), N0, M0 or as any pT (any grade of tumor), N+ (involvement of nearby nodes), M0. Patients who had disease categorized as M1 (metastasis in distant organ or tissue) NED (no evidence of disease) presented not only with the primary kidney tumor but also with solid, isolated, soft-tissue metastases that were completely resected at the time of nephrectomy (synchronous) or at 1 year or less after nephrectomy (metachronous). Five patients in the M0 intermediate-to-high risk group had T2 (grade ≤3 tumor), N0, M0 disease or T1 (tumor in kidney only of ≤7 cm in the greatest dimension), N0, M0 disease; these were protocol violations.
⁋ Sites of metastasis in the subgroup of patients with M1 NED status at baseline are listed in Table S2. ‖ The programmed death ligand 1 (PD-L1) combined positive score was defined as the number of PD-L1– staining cells (tumor cells, lymphocytes, and macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Patient inclusion criteria1
In KEYNOTE-564, the majority of patients studied were at intermediate-high risk of recurrence post-nephrectomy
Exclusion criteria: Patients with active autoimmune disease or a medical condition that required
immunosuppression were ineligible.
pT = primary tumor; M0 = no metastasis; M1 = distant metastasis; N0 = no regional lymph node metastasis; N1 = involvement of regional lymph nodes; NED = no evidence of disease; pT: Primary Tumor Stage
Study population characteristics1
In KEYNOTE-564, the majority of patients studied were at intermediate-hight risk of recurrence post-nephrectomy
- Median age: 60 years (range: 25 to 84 years), 33% aged 65 years or older
- Male: 71%
- ECOG PS of 0: 85%; ECOG PS of 1: 15%
- N0: 94%
- No sarcomatoid features: 84%
86% of patients in KEYNOTE-564 were intermediate-high risk (pT2 with Grade 4 or sarcomatoid features or pT3)
ECOG PS = Eastern Cooperative Oncology Group Performance Status; M1 = distant metastasis; N0 = no
regional lymph node metastasis; NED = no evidence of disease; pT: Primary Tumor Stage
Consider KEYTRUDA® for certain patients at higher risk of recurrence following nephrectomy
If your patient meets any one of these criteria following their nephrectomy…
| Histology | Node | Metastasis | Tumor |
|---|---|---|---|
| pT2 with Grade 4 or sarcomatoid features, N0, M0 | Yes with M0 | M1 NED | pT3 or pT4 with N0, M0 |
You may consider KEYTRUDA®
M0 = no metastasis; M1 = distant metastasis; N0 = no regional lymph node metastasis; N1 = involvement of regional lymph nodes; NED = no evidence of disease; pT: Primary Tumor Stage
KEYTRUDA® significantly reduced the risk of disease recurrence or death compared with placebo.1
KEYNOTE-564: disease-free survival (DFS)1
Median patient follow-up time was 30.1 months (range: 20.8 to 47.5 months)
aHR based on the stratified Cox proportional hazard model.
bP value based on stratified log-rank test.
CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS: overall survival
KEYNOTE-564: overall survival (OS)
Median patient follow-up time was 30.1 months (range: 20.8 to 47.5 months)
CI = confidence interval; HR = hazard ratio; NR = not reached; OS: overall survival.
P-value did not cross the prescribed boundary for statistical significance of 0.000095 (one-sided).
Final analysis for OS to occur after approximately 200 OS events; only 66 events had accrued for this updated analysis.
aDid not cross prespecified p-value boundary for statistical significance of 0.0000093 for 51 events. Final analysis for OS to occur after approximately 200 OS events. Data cutoff date: June 14, 2021.
Adverse Events with an Incidence ≥10% in Either Group (As-Treated Population)1
No adverse events of grade 4 or 5 occurred in at least 10 % of the patients in either group.
A total of 994 patients were randomized to receive either adjuvant pembrolizumab (496
patients) or placebo (498 patients) (intent-to-treat population). A total of 488 patients received
at least 1 dose of KEYTRUDA®, and 496 received at least 1 dose of placebo (as-treated
population).
- Safety was assessed in all the patients who received at least 1 dose of KEYTRUDA® or placebo.
- The median duration of exposure to KEYTRUDA® was 11.1 months (range: 0.0 to 14.3 months) vs 11.1 months (range: 0.0 to 15.4 months) with placebo.
- In the as-treated population, 96.3% of patients in the KEYTRUDA® arm had AEs of any grade and of any cause vs 91.1% in the placebo arm.
- In total, 32.4% of the patients who received KEYTRUDA® and 17.7% of those who received placebo had an AE of Grade 3 to 5.
- 24-month DFS rate: 77.3% (95% CI, 72.8 to 81.1) with KEYTRUDA® vs 68.1% (95% CI, 63.5 to 72.2) with placebo
- 79.1% of patients had treatment-related AEs in the KEYTRUDA® arm (18.9% of these patients had Grade 3–5) vs 53.4% in the placebo arm (1.2% Grade 3–5).
- In the as-treated population, 20.7% of patients in the KEYTRUDA® arm vs 2.0% in the placebo arm discontinued treatment due to AEs.
AE = adverse event
- SmPC Keytruda, 01/2022
