KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
KEYTRUDA + axitinib in first-line treatment of aRCC
From The New England Journal of Medicine, Rini BI, Plimack ER, Stus V, et al; for the KEYNOTE-426 Investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma, 2019;380:1116–1127. Copyright © 2019 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
- Events observed: 59/432 (14%) with KEYTRUDA + axitinib vs 97/429 (23%) with sunitinib
- Median OS not reached with KEYTRUDA + axitinib or with sunitinib
aBased on the stratified Cox proportional hazard model.
bBased on stratified log-rank test.
cP value (one-sided) is compared with the allocated alpha of 0.0001 for this interim analysis (with 39% of the planned number of events for final analysis).
aRCC = advanced RCC; HR = hazard ratio; CI = confidence interval.
- Reduced risk of death by nearly half vs sunitinib
- HRd=0.53; 95% CI, 0.38–0.74; Pe<0.0001f
- Events observed: 59/432 (14%) with KEYTRUDA + axitinib vs 97/429 (23%) with sunitinib
- Median OS not reached with KEYTRUDA + axitinib or with sunitinib
- PFS: HRd=0.69 (95% CI, 0.56–0.84; Pe=0.0001g)
- Events observed: 183/432 (42%) with KEYTRUDA + axitinib vs 213/429 (50%) with sunitinib
- Median PFS: 15.1 months (95% CI,12.6–17.7) with KEYTRUDA + axitinib vs 11.0 months (95% CI, 8.7–12.5) with sunitinib
- ORRh: 59% (95% CI, 54–64) vs 36% ORR with sunitinib (95% CI, 31–40; Pi<0.0001)
- 6% CR and 53% PR for KEYTRUDA + axitinib vs 2% CR and 34% PR for sunitinib
dBased on the stratified Cox proportional hazard model.
eBased on stratified log-rank test.
fP value (one-sided) is compared with the allocated alpha of 0.0001 for this interim analysis (with 39% of the planned number of events for final analysis).
gP value (one-sided) is compared with the allocated alpha of 0.0013 for this interim analysis (with 81% of the planned number of events for final analysis).
hBest objective response as confirmed complete response or partial response.
iBased on Miettinen and Nurminen method stratified by IMDC risk group and geographic region.
PFS = progression-free survival; ORR = objective response rate; CR = complete response; PR = partial response; IMDC = International Metastatic RCC Database Consortium.
KEYTRUDA + axitinib in first-line treatment of aRCC
- Median overall survival for KEYTRUDA + axitinib was not reached vs 35.7 months for sunitinib (95% CI, 33.3–NR).3
LIMITATIONS:
This protocol-specified analysis occurred after an interim analysis that demonstrated the superiority of KEYTRUDA + axitinib in overall survival, progression-free survival, and overall response rate compared to sunitinib alone. No formal statistical testing was performed for the updated analysis, and, therefore, no conclusions can be drawn.3
jHR based on the stratified Cox proportional hazard model.
NR = not reached.
LIMITATIONS:
This protocol-specified analysis occurred after an interim analysis that demonstrated the superiority of KEYTRUDA + axitinib in overall survival, progression-free survival, and overall response rate compared to sunitinib alone. No formal statistical testing was performed for the updated analysis, and, therefore, no conclusions can be drawn.3
- Patients with active autoimmune disease requiring systemic immunosuppression within the last 2 years were ineligible.
- Administration of KEYTRUDA + axitinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator.
- Assessment of tumor status was performed at baseline, after randomization at Week 12, then every 6 weeks thereafter until Week 54, and then every 12 weeks thereafter.
- Patients who tolerated axitinib 5 mg twice daily for 2 consecutive cycles (6 weeks) could increase to 7 mg and then subsequently to 10 mg twice daily.
- Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity.
lRandomization was stratified by IMDC risk categories (favorable vs intermediate vs poor) and geographic region (North America vs Western Europe vs rest of the world.)
Q3W = every 3 weeks; bid = twice daily; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1; BICR = blinded independent central review.
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
Category 1 = Based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.4
Category 2A = Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.4
Preferred intervention = Intervention that is based on superior efficacy, safety, and evidence; and, when appropriate, affordability.4
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.