Who is the adjuvant RCC patient?

KEYTRUDA® (pembrolizumab)
Who is the adjuvant RCC patient?

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland) [External links]

If your patient meets ANY ONE of these criteria following nephrectomy, consider KEYTRUDA instead of active surveillance alone. 2

Intermediate-high risk

pT2 with Grade 4 or sarcomatoid, N0, M0

pT3, any grade, N0, M0

High risk

pT4, any grade, N0, M0

Any pT, any grade with node positive, M0

M1 NED

M1
No evidence of disease (NED) after resection of oligometastatic sites ≤1 year from nephrectomy

KEYTRUDA reduced the risk of disease recurrence or death vs. placebo after nephrectomy2,3

Kaplan-Meier estimate of disease-free survival in KEYNOTE-564 (primary endpoint met, ITT population, 24.1 month median follow-up)2

Disease free survival at 12 months KEYTRUDA 86% vs Placebo 76%. At 24 months KEYTRUDA 77% vs Placebo 68%

Adapted from Choueri TK et al. N Engl J Med. 2021;385(8):683–694.

  • 32% reduction in the risk of disease recurrence or death with KEYTRUDA vs. placebo2
  • Events observed: 109/496 (22%) with KEYTRUDA vs. 151/498 (30%) with placebo. Of these 260 events, 51 deaths had occurred and 209 patients had disease recurrence2
  • Median DFS: not reached for either trial arm2
  • 12-month DFS rate: 86% (95% CI, 82–89) with KEYTRUDA vs. 76% (95% CI, 72–80) with placebo2
  • 24-month DFS rate: 77% (95% CI, 73–81) with KEYTRUDA vs. 68% (95% CI, 63–72) with placebo2

Primary analysis data cutoff date: December 14 2020.2
*Based on the stratified Cox proportional hazard model.2
**Time point was not part of the prespecified analysis and therefore a statistically significant conclusion cannot be drawn.
†Based on stratified log-rank test.2
‡P-value boundary for significance was 0.0114 (one-sided).2

Kaplan-Meier estimate of disease-free survival in KEYNOTE-564 (ITT population, 30.1 month median follow-up)3*

Disease free survival at 30 months KEYTRUDA 78% vs Placebo 67%

Adapted from Choueri TK et al. Presented at ASCO 2022. J Clin Oncol. 2022;40:6 suppl:290-290.

  • 37% reduction in the risk of disease recurrence or death with KEYTRUDA vs. placebo3
  • Events observed: 114/496 (23%) with KEYTRUDA vs. 168/498 (34%) with placebo3
  • Median DFS: Not reached for either trial arm3

Updated analysis data cutoff: June 14, 2021. This was an unplanned update to demonstrate the continued efficacy of KEYTRUDA.3
*At the time of analysis, OS results were not yet mature, as only 33% of deaths needed for the final analysis had accrued at data cutoff.3
**Time point was not part of the prespecified analysis and therefore a statistically significant conclusion cannot be drawn.

Interim overall survival with KEYTRUDA vs. placebo after nephrectomy2,3

Kaplan-Meier estimate of overall survival in interim analysis of KEYNOTE-564 (secondary endpoint, ITT population, 24.1 month median follow-up)2

Overall survival at 24 months KEYTRUDA 97% vs Placebo 94%

Adapted from Choueri TK et al. N Engl J Med. 2021;385(8):683–694.

  • 46% reduction in the risk of death with KEYTRUDA vs. placebo2
  • At the time of analysis, OS results were not yet mature, with 18 deaths out of 496 patients in the KEYTRUDA arm and 33 deaths out of 498 patients in the placebo arm2

Primary analysis data cutoff date: December 14, 2020.2
*Did not cross prespecified p-value boundary for statistical significance.

Kaplan-Meier estimate of overall survival in interim analysis of KEYNOTE-564 (secondary endpoint, ITT population, 30.1 month median follow-up)3

Overall survival at 30 months KEYTRUDA 96% vs Placebo 94%

Adapted from Choueri TK et al. Presented at ASCO 2022. J Clin Oncol. 2022;40:6 suppl:290-290.3
**Time point was not part of the prespecified analysis and therefore a statistically significant conclusion cannot be drawn.

  • 48% reduction in the risk of death with KEYTRUDA vs. placebo3
  • Median OS has yet to be reached in both treatment arms3
  • At the time of analysis, 23 patients in the KEYTRUDA group had an OS event compared to 43 patients in the placebo group. OS results were not yet mature, as only 33% of deaths needed for the final analysis had accrued at data cutoff3

Updated analysis data cutoff date: June 14, 2021.3
*Did not cross prespecified p-value boundary for statistical significance.3

Patients demonstrate a manageable safety profile2,3

Treatment related adverse events with an incidence of ≥5% in either group (as-treated population)4

Treatment related AEs at 24 months tornado chart

Adapted from Choueri TK et al. Presented at ASCO 2021 N Engl J Med. 2021;385(8):683–694.

  • The median duration of exposure to KEYTRUDA was 11.1 months (0.0–14.3 months) vs. 11.1 months (0.0–15.4 months) with placebo2
  • 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 arm2
  • In total, 32.5% of patients who received KEYTRUDA and 17.7% of those who received placebo had an AE of Grade 3 to 52
  • 79.1% of patients had treatment-related AEs in the KEYTRUDA arm (18.9% of these patients had Grade 3 to 4) vs. 53.4% in the placebo arm (1.2% Grade 3 to 4)2
  • In the as-treated population, 20.7% of patients in the KEYTRUDA arm vs. 2.0% in the placebo arm discontinued treatment due to AEs2

Primary analysis data cutoff date: December 14, 2020.2
Median follow up was 24.1 months in this analysis.2
*At the time of analysis, OS results were not yet mature, with 18 deaths out of 496 patients in the KEYTRUDA arm and 33 deaths out of 498 patients in the placebo arm.2

Treatment related adverse events with an incidence of ≥5% in either group (as-treated population)5

Treatment related AEs at 30 months tornado chart

Adapted from Choueri TK et al. Presented at ASCO 2022. J Clin Oncol. 2022;40:6 suppl:290-290.

  • The median duration of exposure to KEYTRUDA was 11.1 months (0.0–14.3 months) vs. 11.1 months (0.0–15.4 months) with placebo3
  • In the as-treated population, 96.3% of patients in the KEYTRUDA arm had AEs of any grade and of any cause vs. 91.3% in the placebo arm3
  • In total, 32.2% of patients who received KEYTRUDA and 17.7% of those who received placebo had an AE of Grade 3 to 53
  • 79.1% of patients had treatment-related AEs in the KEYTRUDA arm (18.6% of these patients had Grade 3 to 4) vs. 53.4% in the placebo arm (1.2% Grade 3 to 4)3
  • In the as-treated population, 21.1% of patients in the KEYTRUDA arm vs 2.2% in the placebo arm discontinued treatment due to AEs3

Updated analysis data cutoff date: June 14, 2021.3
Median follow up was 30.1 months in this analysis.3

Any Grade immune-related adverse events occurring in ≥1% of patients (as-treated population)6

Adverse events table

*The as-treated population was defined as all patients who received at least 1 dose of study drug treatment.6
†No Grade 5 immune-mediated adverse events occurred.6
‡Based on a prespecified list of terms included regardless of attribution to study treatment by investigator.6
§Infusion reactions of any Grade and Grade 3–4 occurred in 7 (1.4%) and 2 patients (0.4%), respectively, with KEYTRUDA and in 5 (1.0%) and no patients, respectively, with placebo.6

Take a closer look: are any of your RCC patients at increased risk of recurrence, suitable for post-nephrectomy adjuvant treatment with KEYTRUDA?

Connect with us
To share your thoughts on these data and arrange a meeting at your convenience, email us at: msdukoncology@msd.com

References

  1. KEYTRUDA Summary of Product Characteristics
  2. Choueri TK et al. N Engl J Med. 2021;385(8):683–694.
  3. Choueri TK et al. J Clin Oncol. 2022;40:6 suppl:290–290.
  4. Adapted from Choueri TK et al. Presented at ASCO 2021. N Engl J Med. 2021;385(8):683–694.
  5. Adapted from Choueri TK et al. Presented at ASCO 2022. J Clin Oncol. 2022;40:6 suppl:290-290.
  6. Choueri TK et al. N Engl J Med. 2021;385(8):683–694. Suppl.

Supporting documentation

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland) 
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GB-RCC-00431 | Date of Preparation: October 2022